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Guo JY, Dong XY, Li S, Tang JF, Zhou CF. Chinese patent medicine: Opening new perspectives for treatment of post-endoscopic submucosal dissection esophageal stricture in esophageal cancer patients. World J Gastroenterol 2025; 31:102943. [PMID: 40248381 PMCID: PMC12001194 DOI: 10.3748/wjg.v31.i14.102943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 02/28/2025] [Accepted: 03/10/2025] [Indexed: 04/11/2025] Open
Abstract
Endoscopic submucosal dissection (ESD) is an effective technique for treating early esophageal cancer, and the prevention of postoperative esophageal stricture has emerged as a significant research topic. Zhou et al utilized an experimental minipig model to demonstrate that Kangfuxin (KFX) can improve postoperative esophageal stricture following ESD by inhibiting transforming growth factor-β1-driven fibrosis and the downstream fibrotic mediators Smad2/3. In this letter, we primarily discuss recent advancements in the treatment of esophageal stricture, the clinical applications of KFX, and the mechanisms involved in alleviating postoperative esophageal stricture, aiming to provide insights for advancing clinical practice and research in esophageal stricture after ESD.
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Affiliation(s)
- Jie-Yu Guo
- School of Life and Health Sciences, Institute of Biomedical Research, Wuhan 430068, Hubei Province, China
| | - Xue-Ying Dong
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, School of Life and Health Sciences, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, Hubei Province, China
| | - Shi Li
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, School of Life and Health Sciences, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, Hubei Province, China
| | - Jing-Feng Tang
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, School of Life and Health Sciences, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, Hubei Province, China
| | - Ce-Fan Zhou
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, School of Life and Health Sciences, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, Hubei Province, China
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Hassanzadeh-Tabrizi SA. Alginate based hemostatic materials for bleeding management: A review. Int J Biol Macromol 2024; 274:133218. [PMID: 38901512 DOI: 10.1016/j.ijbiomac.2024.133218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 06/04/2024] [Accepted: 06/15/2024] [Indexed: 06/22/2024]
Abstract
Severe bleeding has caused significant financial losses as well as a major risk to the lives and health of military and civilian populations. Under some situations, the natural coagulation mechanism of the body is unable to achieve fast hemostasis without the use of hemostatic drugs. Thus, the development of hemostatic materials and techniques is essential. Improving the quality of life and survival rate of patients and minimizing bodily damage requires fast, efficient hemostasis and prevention of bleeding. Alginate is regarded as an outstanding hemostatic polymer because of its non-immunogenicity, biodegradability, good biocompatibility, simple gelation, non-toxicity, and easy availability. This review summarizes the basics of hemostasis and emphasizes the recent developments regarding alginate-based hemostatic systems. Structural modifications and mixing with other materials have widely been used for the improvement of hemostatic characteristics of alginate and for making multifunctional medical devices that not only prevent uncontrolled bleeding but also have antibacterial characteristics, drug delivery abilities, and curing effects. This review is hoped to prepare critical insights into alginate modifications for better hemostatic properties.
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Affiliation(s)
- S A Hassanzadeh-Tabrizi
- Advanced Materials Research Center, Department of Materials Engineering, Najafabad Branch, Islamic Azad University, Najafabad, Iran.
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3
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Wen W, Ertas YN, Erdem A, Zhang Y. Dysregulation of autophagy in gastric carcinoma: Pathways to tumor progression and resistance to therapy. Cancer Lett 2024; 591:216857. [PMID: 38583648 DOI: 10.1016/j.canlet.2024.216857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 03/22/2024] [Accepted: 04/02/2024] [Indexed: 04/09/2024]
Abstract
The considerable death rates and lack of symptoms in early stages of gastric cancer (GC) make it a major health problem worldwide. One of the most prominent risk factors is infection with Helicobacter pylori. Many biological processes, including those linked with cell death, are disrupted in GC. The cellular "self-digestion" mechanism necessary for regular balance maintenance, autophagy, is at the center of this disturbance. Misregulation of autophagy, however, plays a role in the development of GC. In this review, we will examine how autophagy interacts with other cell death processes, such as apoptosis and ferroptosis, and how it affects the progression of GC. In addition to wonderful its role in the epithelial-mesenchymal transition, it is engaged in GC metastasis. The role of autophagy in GC in promoting drug resistance stands out. There is growing interest in modulating autophagy for GC treatment, with research focusing on natural compounds, small-molecule inhibitors, and nanoparticles. These approaches could lead to breakthroughs in GC therapy, offering new hope in the fight against this challenging disease.
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Affiliation(s)
- Wen Wen
- Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Liaoning Clinical Research Center for Laboratory Medicine, Shenyang, China
| | - Yavuz Nuri Ertas
- Department of Biomedical Engineering, Erciyes University, Kayseri, Turkey; ERNAM-Nanotechnology Research and Application Center, Erciyes University, Kayseri, Turkey.
| | - Ahmet Erdem
- Institute for Quantitative Health Science and Engineering (IQ), Department of Biomedical Engineering, College of Engineering and Human Medicine, Michigan State University, East Lansing, MI, 48824, USA; Department of Biomedical Engineering, Kocaeli University, Umuttepe Campus, Kocaeli, 41001 Turkey.
| | - Yao Zhang
- Department of Gynaecology, Shengjing Hospital of China Medical University, Shenyang, China.
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4
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Lin X, Chu J, Xiang Y, He M, Ma Q, Duan J, Wang Y, Sun S. Kangfuxin liquid reduces the ultraviolet B-induced photodamage of HaCaT cells by regulating autophagy. Biosci Biotechnol Biochem 2023; 87:1485-1494. [PMID: 37682519 DOI: 10.1093/bbb/zbad130] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 08/31/2023] [Indexed: 09/09/2023]
Abstract
Kangfuxin liquid (KFX), an extract of the American cockroach, has been clinically proven to be effective in various skin damage disorders, but there are no reports on its use in photodamage. We explored the effect of KFX on ultraviolet B (UVB)-induced photodamage and whether its mechanism was related to autophagy. We found that KFX treatment reduced UVB-induced reactive oxygen species production and improved the vitality of cells inhibited by UVB irradiation. The expression of LC3 (A/B), which was inhibited after UVB irradiation, could be rescued by KFX treatment. Furthermore, KFX may upregulate the level of cellular autophagy by regulating the AMPK-mTOR signaling pathway. When the autophagy inhibitor wortmannin was used to inhibit autophagy, the protective effect of KFX on cells was diminished or even disappeared. Our study suggests that KFX may resist UVB-mediated oxidative stress damage of HaCaT through the induction of autophagy.
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Affiliation(s)
- Xianghong Lin
- College of Clinical Medicine, Dali University, Dali, Yunnan, China
| | - Jimin Chu
- Department of Skin Medical Beauty, People's Hospital of Pengshui County, Pengshui, Chongqing, China
| | - Yang Xiang
- Key Laboratory of Human Aging in Jiangxi Province, Nanchang University, Nanchang, Jiangxi, China
| | - Miao He
- College of Pharmacy and Chemistry, Dali University, Dali, Yunnan, China
| | - Qiong Ma
- Department of Medical Cosmetology, The First Affiliated Hospital of Dali University, Dali, Yunnan, China
| | - Jingxian Duan
- Department of Medical Cosmetology, The First Affiliated Hospital of Dali University, Dali, Yunnan, China
| | - Yan Wang
- Department of Medical Cosmetology, The First Affiliated Hospital of Dali University, Dali, Yunnan, China
| | - Sujiao Sun
- Department of Medical Cosmetology, The First Affiliated Hospital of Dali University, Dali, Yunnan, China
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Zhang JX, Yuan WC, Li CG, Zhang HY, Han SY, Li XH. A review on the mechanisms underlying the antitumor effects of natural products by targeting the endoplasmic reticulum stress apoptosis pathway. Front Pharmacol 2023; 14:1293130. [PMID: 38044941 PMCID: PMC10691277 DOI: 10.3389/fphar.2023.1293130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 10/27/2023] [Indexed: 12/05/2023] Open
Abstract
Cancer poses a substantial risk to human life and wellbeing as a result of its elevated incidence and fatality rates. Endoplasmic reticulum stress (ERS) is an important pathway that regulates cellular homeostasis. When ERS is under- or overexpressed, it activates the protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)-, inositol-requiring enzyme 1 (IRE1)- and activating transcription Factor 6 (ATF6)-related apoptotic pathways to induce apoptosis. Tumor cells and microenvironment are susceptible to ERS, making the modulation of ERS a potential therapeutic approach for treating tumors. The use of natural products to treat tumors has substantially progressed, with various extracts demonstrating antitumor effects. Nevertheless, there are few reports on the effectiveness of natural products in inducing apoptosis by specifically targeting and regulating the ERS pathway. Further investigation and elaboration of its mechanism of action are still needed. This paper examines the antitumor mechanism of action by which natural products exert antitumor effects from the perspective of ERS regulation to provide a theoretical basis and new research directions for tumor therapy.
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Affiliation(s)
- Jie-Xiang Zhang
- The First Clinical College of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Wei-Chen Yuan
- Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor, The First Clinical College of Nanjing University of Chinese Medicine, Nanjing, China
- The College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Cheng-Gang Li
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Hai-Yan Zhang
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Shu-Yan Han
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Integration of Chinese and Western Medicine, Peking University Cancer Hospital and Institute, Beijing, China
| | - Xiao-Hong Li
- Shandong University of Traditional Chinese Medicine, Jinan, China
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Zhao B, Zhang Y, Xu J, Li Y, Yuan Q, Zhou C. Periplaneta Americana extract inhibits osteoclastic differentiation in vitro. Cell Prolif 2023; 56:e13341. [PMID: 36210640 PMCID: PMC9890529 DOI: 10.1111/cpr.13341] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 09/01/2022] [Accepted: 09/07/2022] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVES Periplaneta americana extract (PAE) is proven to be promising in treating fever, wound healing, liver fibrosis, and cardiovascular disease. However, the role of PAE in skeletal disorders remains unclear. This study investigated whether PAE regulates osteoclastic differentiation in vitro via the culture using RAW264.7 cells and bone marrow derived macrophages (BMDMs). MATERIALS AND METHODS RAW264.7 cells and BMDMs were cultured and induced for osteoclastic differentiation supplementing with different concentrations of PAE (0, 0.1, 1, and 10 mg/mL). Cell counting kit-8 (CCK-8) assay was used to detect the cytotoxicity and cell proliferation. TRAP staining, actin ring staining, real-time quantitative PCR (RT-qPCR), and bone resorption activity test were performed to detect osteoclastic differentiation. RT-qPCR and enzyme-linked immunosorbent assay (ELISA) were conducted to assay the expression and secretion of inflammatory factors. RNA sequencing (RNA-seq) and western blot analysis were carried out to uncover the underlying mechanism. RESULTS CCK-8 results showed that 10 mg/mL and a lower concentration of PAE did not affect cell proliferation. RT-qPCR analysis verified that PAE down-regulated the osteoclastic genes Nfatc1, Ctsk, and Acp5 in macrophages. Moreover, PAE restrained the differentiation, formation, and function of osteoclasts. Besides, RT-qPCR and ELISA assays showed that PAE decreased inflammatory genes expression and reduced the secretion of inflammatory factors, including IL1β, IL6, and TNFα. Subsequent RNA-seq analysis identified possible genes and signaling pathways of PAE-mediated osteoclastogenesis suppression. CONCLUSIONS Our study indicates that PAE has inhibitive effects on osteoclastogenesis and may be a potential therapeutic alternative for bone diseases.
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Affiliation(s)
- Bin Zhao
- State Key Laboratory of Oral Diseases, National Clinical Research Centre for Oral Disease, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Yuning Zhang
- State Key Laboratory of Oral Diseases, National Clinical Research Centre for Oral Disease, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Jie Xu
- State Key Laboratory of Oral Diseases, National Clinical Research Centre for Oral Disease, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Yuyu Li
- State Key Laboratory of Oral Diseases, National Clinical Research Centre for Oral Disease, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Quan Yuan
- State Key Laboratory of Oral Diseases, National Clinical Research Centre for Oral Disease, West China Hospital of StomatologySichuan UniversityChengduChina
- Department of Oral Implantology, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Chenchen Zhou
- State Key Laboratory of Oral Diseases, National Clinical Research Centre for Oral Disease, West China Hospital of StomatologySichuan UniversityChengduChina
- Department of Pediatric Dentistry, West China Hospital of StomatologySichuan UniversityChengduChina
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Rahman MA, Ahmed KR, Rahman MDH, Park MN, Kim B. Potential Therapeutic Action of Autophagy in Gastric Cancer Managements: Novel Treatment Strategies and Pharmacological Interventions. Front Pharmacol 2022; 12:813703. [PMID: 35153766 PMCID: PMC8834883 DOI: 10.3389/fphar.2021.813703] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 12/13/2021] [Indexed: 12/11/2022] Open
Abstract
Gastric cancer (GC), second most leading cause of cancer-associated mortality globally, is the cancer of gastrointestinal tract in which malignant cells form in lining of the stomach, resulting in indigestion, pain, and stomach discomfort. Autophagy is an intracellular system in which misfolded, aggregated, and damaged proteins, as well as organelles, are degraded by the lysosomal pathway, and avoiding abnormal accumulation of huge quantities of harmful cellular constituents. However, the exact molecular mechanism of autophagy-mediated GC management has not been clearly elucidated. Here, we emphasized the role of autophagy in the modulation and development of GC transformation in addition to underlying the molecular mechanisms of autophagy-mediated regulation of GC. Accumulating evidences have revealed that targeting autophagy by small molecule activators or inhibitors has become one of the greatest auspicious approaches for GC managements. Particularly, it has been verified that phytochemicals play an important role in treatment as well as prevention of GC. However, use of combination therapies of autophagy modulators in order to overcome the drug resistance through GC treatment will provide novel opportunities to develop promising GC therapeutic approaches. In addition, investigations of the pathophysiological mechanism of GC with potential challenges are urgently needed, as well as limitations of the modulation of autophagy-mediated therapeutic strategies. Therefore, in this review, we would like to deliver an existing standard molecular treatment strategy focusing on the relationship between chemotherapeutic drugs and autophagy, which will help to improve the current treatments of GC patients.
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Affiliation(s)
- Md. Ataur Rahman
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- Department of Biotechnology and Genetic Engineering, Global Biotechnology and Biomedical Research Network (GBBRN), Faculty of Biological Sciences, Islamic University, Kushtia, Bangladesh
| | - Kazi Rejvee Ahmed
- Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia, Bangladesh
| | - MD. Hasanur Rahman
- Department of Biotechnology and Genetic Engineering, Global Biotechnology and Biomedical Research Network (GBBRN), Faculty of Biological Sciences, Islamic University, Kushtia, Bangladesh
- ABEx Bio-Research Center, East Azampur, Bangladesh
| | - Moon Nyeo Park
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - Bonglee Kim
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
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de Seabra Rodrigues Dias IR, Lo HH, Zhang K, Law BYK, Nasim AA, Chung SK, Wong VKW, Liu L. Potential therapeutic compounds from traditional Chinese medicine targeting endoplasmic reticulum stress to alleviate rheumatoid arthritis. Pharmacol Res 2021; 170:105696. [PMID: 34052360 DOI: 10.1016/j.phrs.2021.105696] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 05/25/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023]
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease which affects about 0.5-1% of people with symptoms that significantly impact a sufferer's lifestyle. The cells involved in propagating RA tend to display pro-inflammatory and cancer-like characteristics. Medical drug treatment is currently the main avenue of RA therapy. However, drug options are limited due to severe side effects, high costs, insufficient disease retardation in a majority of patients, and therapeutic effects possibly subsiding over time. Thus there is a need for new drug therapies. Endoplasmic reticulum (ER) stress, a condition due to accumulation of misfolded proteins in the ER, and subsequent cellular responses have been found to be involved in cancer and inflammatory pathologies, including RA. ER stress protein markers and their modulation have therefore been suggested as therapeutic targets, such as GRP78 and CHOP, among others. Some current RA therapeutic drugs have been found to have ER stress-modulating properties. Traditional Chinese Medicines (TCMs) frequently use natural products that affect multiple body and cellular targets, and several medicines and/or their isolated compounds have been found to also have ER stress-modulating capabilities, including TCMs used in RA treatment by Chinese Medicine practitioners. This review encourages, in light of the available information, the study of these RA-treating, ER stress-modulating TCMs as potential new pharmaceutical drugs for use in clinical RA therapy, along with providing a list of other ER stress-modulating TCMs utilized in treatment of cancers, inflammatory diseases and other diseases, that have potential use in RA treatment given similar ER stress-modulating capacity.
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Affiliation(s)
- Ivo Ricardo de Seabra Rodrigues Dias
- Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology, Macau, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
| | - Hang Hong Lo
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
| | - Kaixi Zhang
- Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology, Macau, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
| | - Betty Yuen Kwan Law
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, China
| | - Ali Adnan Nasim
- Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology, Macau, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
| | - Sookja Kim Chung
- Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology, Macau, China; Faculty of Medicine, Macau University of Science and Technology, Macau, China.
| | - Vincent Kam Wai Wong
- Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology, Macau, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, China.
| | - Liang Liu
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, China.
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Tian M, Dong J, Wang Z, Lu S, Geng F. The effects and mechanism of Kangfuxin on improving healing quality and preventing recurrence of gastric ulcer. Biomed Pharmacother 2021; 138:111513. [PMID: 33761454 DOI: 10.1016/j.biopha.2021.111513] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 02/24/2021] [Accepted: 03/11/2021] [Indexed: 02/06/2023] Open
Abstract
This study investigated the gastroprotective effects and possible mechanism of Kangfuxin (KFX), an ethanol extract of Periplaneta americana L. (Dictyoptera; Blattidae), on improving healing quality and preventing recurrence of gastric ulcer. The effects of KFX were investigated in patients treated with endoscopic submucosal dissection (ESD), gastric ulcer animal model, and rat gastric mucosal cells and fibroblasts. Moreover, the relationship between KFX and p38/NF-κB pathway were explored both in vivo and in vitro. In patients, KFX exhibited protective effects against gastric ulcers and resulted in a decrease in the CD3 expression. In vivo animal experiments confirmed that KFX accelerated ulcer healing by promoting neovascularization (increased CD34 expression), suppressing inflammation (decreased interleukin-1β (IL-1β), myeloperoxidase (MPO), tumor necrosis factor α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and IL-8 expression), and enhancing growth factor expression, including the epidermal growth factor receptor (EGFR) and hepatocyte growth factor (HGF). In vitro experiments demonstrated that treatment with 10% KFX rat serum decreased IL-1β, IL-1Ra, SIL-1RAP, TNF-α, and ICAM-1 expression in rat gastric mucosal cells or fibroblasts and increased IL-1R expression compared to that in the group treatment with 10% normal rat serum. Furthermore, KFX inhibited the activation of p38/NF-κB pathway both in vivo and in vitro. In conclusion, KFX treatment could effectively improve healing quality and prevent gastric ulcer recurrence, which might be attributed to neovascularization, suppressed inflammation, and enhanced growth factor expression. The p38/NF-κB pathway may be one of important mechanism to mediate the effects of KFX.
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Affiliation(s)
- Ming Tian
- Shanghai Burn Institute, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Jiaoyun Dong
- Shanghai Burn Institute, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Zhengting Wang
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Shuliang Lu
- Shanghai Burn Institute, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
| | - Funeng Geng
- Sichuan Key Laboratory of Medical American Cockroach, Chengdu, Sichuan 610000, China.
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Spirina LV, Avgustinovich AV, Afanas'ev SG, Cheremisina OV, Volkov MY, Choynzonov EL, Gorbunov AK, Usynin EA. Molecular Mechanism of Resistance to Chemotherapy in Gastric Cancers, the Role of Autophagy. Curr Drug Targets 2021; 21:713-721. [PMID: 31775598 DOI: 10.2174/1389450120666191127113854] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 11/11/2019] [Accepted: 11/21/2019] [Indexed: 12/13/2022]
Abstract
Gastric cancer (GC) is biologically and genetically heterogeneous with complex carcinogenesis at the molecular level. Despite the application of multiple approaches in the GC treatment, its 5-year survival is poor. A major limitation of anti-cancer drugs application is intrinsic or acquired resistance, especially to chemotherapeutical agents. It is known that the effectiveness of chemotherapy remains debatable and varies according to the molecular type of GC. Chemotherapy has an established role in the management of GC. Perioperative chemotherapy or postoperative chemotherapy is applied for localized ones. Most of the advanced GC patients have a poor response to treatment and unfavorable outcomes with standard therapies. Resistance substantially limits the depth and duration of clinical responses to targeted anticancer therapies. Through the use of complementary experimental approaches, investigators have revealed that cancer cells can achieve resistance through adaptation or selection driven by specific genetic, epigenetic, or microenvironmental alterations. Ultimately, these diverse alterations often lead to the activation of MAPK, AKT/mTOR, and Wnt/β-catenin signaling pathways that, when co-opted, enable cancer cells to survive drug treatments. We have summarized the mechanisms of resistance development to cisplatin, 5-fluorouracil, and multidrug resistance in the GC management. The complexity of molecular targets and components of signaling cascades altered in the resistance development results in the absence of significant benefits in GC treatment, and its efficacy remains low. The universal process responsible for the failure in the multimodal approach in GC treatment is autophagy. Its dual role in oncogenesis is the most unexplored issue. We have discussed the possible mechanism of autophagy regulation upon the action of endogenous factors and drugs. The experimental data obtained in the cultured GC cells need further verification. To overcome the cancer resistance and to prevent autophagy as the main reason of ineffective treatment, it is suggested the concept of the direct influence of autophagy molecular markers followed by the standard chemotherapy. Dozen of studies have focused on finding the rationale for the benefits of such complex therapy. The perspectives in the molecular-based management of GC are associated with the development of molecular markers predicting the protective autophagy initiation and search for novel targets of effective anticancer therapy.
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Affiliation(s)
- Liudmila V Spirina
- Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 5 Koopertivny street, Tomsk, 634050, Russian Federation.,Siberian State Medical University, 2, Moskovsky trakt, Tomsk, 634050, Russian Federation
| | - Alexandra V Avgustinovich
- Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 5 Koopertivny street, Tomsk, 634050, Russian Federation
| | - Sergey G Afanas'ev
- Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 5 Koopertivny street, Tomsk, 634050, Russian Federation
| | - Olga V Cheremisina
- Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 5 Koopertivny street, Tomsk, 634050, Russian Federation
| | - Maxim Yu Volkov
- Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 5 Koopertivny street, Tomsk, 634050, Russian Federation
| | - Evgeny L Choynzonov
- Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 5 Koopertivny street, Tomsk, 634050, Russian Federation.,Siberian State Medical University, 2, Moskovsky trakt, Tomsk, 634050, Russian Federation
| | - Alexey K Gorbunov
- Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 5 Koopertivny street, Tomsk, 634050, Russian Federation
| | - Evgeny A Usynin
- Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 5 Koopertivny street, Tomsk, 634050, Russian Federation.,Siberian State Medical University, 2, Moskovsky trakt, Tomsk, 634050, Russian Federation
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11
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Courtois S, Haykal M, Bodineau C, Sifré E, Azzi-Martin L, Ménard A, Mégraud F, Lehours P, Durán RV, Varon C, Bessède E. Autophagy induced by Helicobacter pylori infection is necessary for gastric cancer stem cell emergence. Gastric Cancer 2021; 24:133-144. [PMID: 32940810 DOI: 10.1007/s10120-020-01118-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Accepted: 07/28/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND The main cause of gastric cancer is the infection by the bacterium Helicobacter pylori which induces a chronic inflammation and an epithelial-to-mesenchymal transition (EMT) leading to the emergence of cells with cancer stem cell (CSC) properties. However, the underlying mechanisms have not been fully characterized. Moreover, H. pylori modulates the host cell autophagic process, but a few studies have investigated the role of this process in tumoral transformation. The aim of this study was to determine whether H. pylori-induced autophagy has a role in CSC emergence. METHODS Autophagic flux in response to H. pylori infection was characterized in AGS cell line expressing the tandem-tagged mCherry-GFP-LC3 protein and using a ratiometric flow cytometry analysis. Then, AGS and MKN45 cell lines were treated with bafilomycin or chloroquine, two pharmaceutical well-known inhibitors of autophagy, and different EMT and CSC characteristics were analyzed. RESULTS First, a co-expression of the gastric CSC marker CD44 and the autophagic marker LC3 in mice and human stomach tissues infected with H. pylori was observed. Then, we demonstrated in vitro that H. pylori was able to activate the autophagy process with a reduced autophagic flux. Finally, infected cells were treated with autophagy inhibitors, which reduced (i) appearance of mesenchymal phenotypes and migration ability related to EMT and (ii) CD44 expression as well as tumorsphere formation capacities reflecting CSC properties. CONCLUSION In conclusion, all these data show that H. pylori-induced autophagy is implicated in gastric CSC emergence and could represent an interesting therapeutic target.
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Affiliation(s)
- Sarah Courtois
- Univ. Bordeaux, INSERM, BaRITOn, U1053, F-33000, Bordeaux, France
| | - Maria Haykal
- Univ. Bordeaux, INSERM, BaRITOn, U1053, F-33000, Bordeaux, France
| | - Clément Bodineau
- Centro Andaluz de Biología Molecular Y Medicina Regenerativa-CABIMER, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Universidad Pablo de Olavide, Américo Vespucio 24, 41092, Sevilla, Spain.,Institut Européen de Chimie et Biologie, INSERM U1218, University of Bordeaux, Pessac, France
| | - Elodie Sifré
- Univ. Bordeaux, INSERM, BaRITOn, U1053, F-33000, Bordeaux, France
| | | | - Armelle Ménard
- Univ. Bordeaux, INSERM, BaRITOn, U1053, F-33000, Bordeaux, France
| | - Francis Mégraud
- Univ. Bordeaux, INSERM, BaRITOn, U1053, F-33000, Bordeaux, France.,French National Reference Center for Campylobacters and Helicobacters (CNRCH), University Hospital of Bordeaux, Place Amelie Raba Leon, 33076, Bordeaux, France
| | - Philippe Lehours
- Univ. Bordeaux, INSERM, BaRITOn, U1053, F-33000, Bordeaux, France.,French National Reference Center for Campylobacters and Helicobacters (CNRCH), University Hospital of Bordeaux, Place Amelie Raba Leon, 33076, Bordeaux, France
| | - Raúl V Durán
- Centro Andaluz de Biología Molecular Y Medicina Regenerativa-CABIMER, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Universidad Pablo de Olavide, Américo Vespucio 24, 41092, Sevilla, Spain
| | - Christine Varon
- Univ. Bordeaux, INSERM, BaRITOn, U1053, F-33000, Bordeaux, France
| | - Emilie Bessède
- Univ. Bordeaux, INSERM, BaRITOn, U1053, F-33000, Bordeaux, France. .,French National Reference Center for Campylobacters and Helicobacters (CNRCH), University Hospital of Bordeaux, Place Amelie Raba Leon, 33076, Bordeaux, France.
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Lin M, Zhang S, Zhang M, Shi J, Zhang C, Luo R, You J, Sun J, Zhang J, Gao F. Therapeutic efficacy and safety of Kangfuxin in combination with rabeprazole in the treatment of peptic ulcer: A systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e23103. [PMID: 33235070 PMCID: PMC7710217 DOI: 10.1097/md.0000000000023103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Kangfuxin (KFX), a well-known Chinese patent medicine which extracted from Periplaneta americana, is widely used as an adjuvant in the treatment of peptic ulcers (PUs) with proton pump inhibitors (PPIs) such as rabeprazole, in China. However, no clear consensus has been reached on the efficacy for PU treatment. METHODS We searched in 7 electronic databases to find randomized controlled trials (RCTs) completed before May 31, 2020 to explore the clinical efficiency of KFX plus rabeprazole in the treatment of PU. Risk ratio (RR) corresponding to 95% confidence interval (CI) was calculated to estimate the outcomes. Publication bias was assessed by both Egger's and Begg's tests. Statistical analyses were performed using RevMan 5.4 and Stata version 10.0. RESULTS Twenty-five RCTs, comprising 2555 PU patients, were included in this study. Meta-analysis showed that, when compared with rabeprazole-based treatment alone, KFX plus rabeprazole significantly improved the healing rate (RR = 1.34, 95% CI 1.25-1.44) and overall response rate of ulcers (RR = 1.16, 95% CI 1.13-1.20), alleviated the clinical symptoms of PU (RR = 1.14, 95% CI 1.08-1.21), and reduced the recurrence of PU (RR = 0.38, 95% CI 0.24-0.61) without an increase in the occurrence of adverse events (RR = 0.92, 95% CI 0.66-1.28). CONCLUSION Our study suggests that KFX combined with rabeprazole showed positive therapeutic effects and is safe for treating PU, which may provide more reliable evidence for the clinical use of KFX in the treatment of PU.
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Affiliation(s)
- Meisi Lin
- Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China and Pharmacy School, Chengdu University of Traditional Chinese Medicine
- Sichuan Acupuncture School, Chengdu
| | - Siyuan Zhang
- Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China and Pharmacy School, Chengdu University of Traditional Chinese Medicine
- Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao
| | - Minyue Zhang
- Division of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai
| | - Jinfeng Shi
- Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China and Pharmacy School, Chengdu University of Traditional Chinese Medicine
| | - Chen Zhang
- Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China and Pharmacy School, Chengdu University of Traditional Chinese Medicine
| | - Ruifeng Luo
- Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China and Pharmacy School, Chengdu University of Traditional Chinese Medicine
| | - Jieshu You
- School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou
| | - Jiayi Sun
- Innovative Institute of Chinese of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jinming Zhang
- Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China and Pharmacy School, Chengdu University of Traditional Chinese Medicine
| | - Fei Gao
- Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China and Pharmacy School, Chengdu University of Traditional Chinese Medicine
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13
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Lu S, Wu D, Sun G, Geng F, Shen Y, Tan J, Sun X, Luo Y. Gastroprotective effects of Kangfuxin against water-immersion and restraint stress-induced gastric ulcer in rats: roles of antioxidation, anti-inflammation, and pro-survival. PHARMACEUTICAL BIOLOGY 2019; 57:770-777. [PMID: 31696757 PMCID: PMC6844415 DOI: 10.1080/13880209.2019.1682620] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/04/2023]
Abstract
Context: Kangfuxin (KFX) is widely used for the treatment of gastric and duodenal ulcer; however, more research is needed to determine the protective mechanisms of KFX in ameliorating gastric ulcer.Objective: To investigate the efficacy and potential mechanism of Kangfuxin liquid (KFX) in water-immersion and restraint stress (WIRS)-induced gastric ulcer.Materials and methods: Seventy rats were randomly divided into seven groups (n = 10) as follows: the control group (normal saline, i.g.), the model group (normal saline, i.g.), the KFX groups (2.5, 5 and 10 mL/kg, i.g.), the omeprazole group (20 mg/kg, i.p.) and Sanjiuweitai Granules group (1850 mg/kg, i.g.). The WIRS model was applied to induce stress ulcers after 7 days of drug administration. Afterwards, rats were sacrificed at 10 h induced by WIRS.Results: Pre-treatment with KFX (5,10 mL/kg) could effectively reduce the area of gastric ulcers and improve the pathological changes of ulcerated tissue. Moreover, KFX (5,10 mL/kg) increased the prostaglandin E2 (52%) and cyclooxygenase-1 (30%) levels, and improved malondialdehyde (54%), superoxide dismutase (58%), catalase (39%), and nitric oxide (11%) and TNF-α (9%), IL-6 (11%), MMP-9 (54%) and MMP-2 (53%) of ulcer tissue. Furthermore, pre-treatment with KFX dramatically increased IGF-1, PTEN, and Akt protein expression.Conclusions: Our results suggest that KFX has protective effects on WIRS-induced gastric ulcer via inflammatory reactions, oxidative stress inhibition, and pro-survival action, which were the results of activating the IGF-1/PTEN/Akt signalling pathway. Our results provide evidence of KFX for treating gastric ulcer.
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Affiliation(s)
- Shan Lu
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China
| | - Daoshun Wu
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China
| | - Guibo Sun
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China
| | - Funeng Geng
- Sichuan Good Doctor Panxi Pharmaceutical Co., LTD., Xichang, China
| | - Yongmei Shen
- Sichuan Good Doctor Panxi Pharmaceutical Co., LTD., Xichang, China
| | - Jin Tan
- Sichuan Good Doctor Panxi Pharmaceutical Co., LTD., Xichang, China
| | - Xiaobo Sun
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China
- Xiaobo Sun Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, China
| | - Yun Luo
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China
- CONTACT Yun Luo
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Zheng Y, Tu J, Wang X, Yu Y, Li J, Jin Y, Wu J. The Therapeutic Effect of Melatonin on GC by Inducing Cell Apoptosis and Autophagy Induced by Endoplasmic Reticulum Stress. Onco Targets Ther 2019; 12:10187-10198. [PMID: 32063713 PMCID: PMC6884966 DOI: 10.2147/ott.s226140] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Accepted: 11/04/2019] [Indexed: 12/24/2022] Open
Abstract
Background Gastric cancer (GC) is the main malignancy affecting a large population worldwide. Lack of effective enough treatment is one of the leading factors contributing to the high mortality rate. Melatonin, a naturally occurring compound, has been proven to exert cytotoxic and antiproliferative effects on human gastric cancers. Nevertheless, the mechanisms of anti-gastric cancer of melatonin remain elucidated. It is believed that endoplasmic reticulum (ER) stress and its resultant unfolded protein response (UPR) are connected to the survival, progression, and chemoresistance of various tumor cells via multiple cellular procedures, such as autophagy. In this study, the effects of melatonin on human gastric cancer cell lines AGS and SGC-7901 was assessed to reveal the interaction between melatonin, endoplasmic reticulum stress, and autophagy in gastric cancer. Methods CCK-8, the wound healing analysis, colony formation assay, immunofluorescence analysis, Western blotting, flow cytometry, and animal models were used in the current study. Results The data demonstrated that melatonin could inhibit GC growth, proliferation, and invasion both in vivo and in vitro. Apoptosis and autophagy induced in a concentration-dependent manner is response to melatonin-induced ER stress. Melatonin induced the expression of apoptotic and autophagy-related proteins, which was markedly attenuated by the ER stress inhibitor 4-PBA and autophagy inhibitor 3-MA. In addition, we used the specific IRE1 inhibitor STF 083010, finding that inhibiting IRE1 could considerably relieve ER stress-induced autophagy activity, as revealed by the reduction of LC3-II and Beclin-1. Conclusion This study confirmed that melatonin-induced inhibition of GC cell proliferation is mediated by the activation of the IRE/JNK/Beclin1 signaling.
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Affiliation(s)
- Yanshan Zheng
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People's Republic of China
| | - Jiawei Tu
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People's Republic of China
| | - Xinxin Wang
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People's Republic of China
| | - Yue Yu
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People's Republic of China
| | - Jiajia Li
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People's Republic of China
| | - Yin Jin
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People's Republic of China
| | - Jiansheng Wu
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People's Republic of China
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15
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Liu H, Mei D, Xu P, Wang H, Wang Y. YAP promotes gastric cancer cell survival and migration/invasion via the ERK/endoplasmic reticulum stress pathway. Oncol Lett 2019; 18:6752-6758. [PMID: 31807184 PMCID: PMC6876304 DOI: 10.3892/ol.2019.11049] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Accepted: 10/03/2019] [Indexed: 12/26/2022] Open
Abstract
Yes-associated protein (YAP) has been reported to serve an important role in gastric cancer cell survival and migration. However, the underlying mechanism remains unclear. The aim of present study was to identify the underlying mechanism through which Yap sustains gastric cancer viability and migration. The results of the present study demonstrated that YAP expression was upregulated in gastric cancer MKN-28/74 cells compared with normal gastric GES-1 cells. Functional studies revealed that silencing of YAP inhibited gastric cancer MKN-28/74 cell viability and invasion. Mechanistically, YAP may promote gastric cancer cell survival and migration/invasion by inhibiting the endoplasmic reticulum (ER) stress pathway. In addition, YAP may regulate ER stress by activating the ERK signaling pathway. The results of the present study suggested that YAP may be a tumor promoter in gastric cancer and act through the ERK/ER stress pathway; therefore, YAP may have potential implications for new approaches to gastric cancer therapy.
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Affiliation(s)
- Haibin Liu
- Department of Gastrointestinal Surgery, China-Japan Friendship Hospital, Beijing 100029, P.R. China
| | - Dong Mei
- Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, Beijing 100045, P.R. China
| | - Pengcheng Xu
- Department of Pharmaceutical Engineering, College of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010110, P.R. China
| | - Haisheng Wang
- Department of Pharmaceutical Engineering, College of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010110, P.R. China
| | - Yan Wang
- Department of Gastrointestinal Surgery, China-Japan Friendship Hospital, Beijing 100029, P.R. China
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16
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Endoplasmic reticulum proteostasis control and gastric cancer. Cancer Lett 2019; 449:263-271. [PMID: 30776479 DOI: 10.1016/j.canlet.2019.01.034] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Revised: 01/16/2019] [Accepted: 01/26/2019] [Indexed: 02/07/2023]
Abstract
The endoplasmic reticulum (ER) is the primary organelle responsible for the synthesis, modification, folding and secretion of proteins, especially in specialized secretory cells. It also contributes to the maintenance of cellular functions, such as Ca2+ storage, lipogenesis, gluconeogenesis, and organelle biogenesis. Cellular stress conditions, such as glucose deprivation, hypoxia and disturbance of Ca2+ homeostasis, may increase the risk of protein misfolding and perturb proteostasis. This activates ER stress and triggers the unfolded protein response (UPR), leading to either the restoration of homeostasis or cell death. ER stress and UPR have been shown to play crucial roles in the pathogenesis, progression and treatment response of various cancers. In gastric cancer (GC), one of the most aggressive cancer types, critical functions of ER stress signaling have also started to emerge. Herein, we summarize the current knowledge linking ER stress and UPR to GC; we also discuss the possible nodes of therapeutic intervention and propose directions of future research.
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Ma X, Sun J, Ye W, Huang Y, Sun C, Tao Y, Wang T, Cong W, Geng F. Pro-apoptotic effects of Kangfuxin on human stomach cancer cells and its underlying mechanism. Oncol Lett 2018; 16:931-939. [PMID: 29963166 PMCID: PMC6019916 DOI: 10.3892/ol.2018.8713] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Accepted: 03/19/2018] [Indexed: 12/11/2022] Open
Abstract
Kangfuxin (KFX) is an oral liquid derived from Periplaneta americana, with complex components. KFX has been demonstrated to exhibit anticancer activity in a variety of different types of tumor, including gastric cancer; however, its underlying molecular mechanism remains unclear. The present study was designed to investigate the pro-apoptotic effects of KFX on SGC-7901 cells, in order to provide a theoretical basis for clinical application. In order to clarify the pro-apoptotic effects of KFX on SGC-7901 cells, MTT analysis was conducted. To evaluate the anticancer effect of KFX, peroxisome proliferator-activated receptor (PPAR)-γ was analyzed by reverse transcription-polymerase chain reaction. Western blot analysis was used to determine the effects of KFX on the expression of cleaved caspase-3, phosphorylated extracellular signal-regulated kinase (p-ERK), ERK, tumor protein p53 (p53), B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X, interleukin (IL)-6 and IL-1β. In addition, terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL) analysis was used to detect apoptosis in SGC-7901 cells. It was revealed that PPAR-γ was increased in SGC-7901 cells following treatment with KFX, shown by an increase in mRNA expression. Furthermore, western blot analysis identified that KFX treatment groups exhibited markedly inhibited levels of Bcl-2, IL-6, IL-1β and p-ERK, and induced p53 protein expression. Additionally, TUNEL and MTT assays demonstrated that treatment with KFX may induce SGC-7901 cell apoptosis and inhibit proliferation. In conclusion, to the best of our knowledge, the results of the present study demonstrated for the first time that KFX may induce SGC-7901 cell apoptosis and inhibit its proliferation, and this may be primarily attributed to its role in mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase/ERK signaling pathway inhibition.
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Affiliation(s)
- Xiuying Ma
- Sichuan Key Laboratory of Medical American Cockroach, Chengdu, Sichuan 610000, P.R. China
| | - Jia Sun
- College of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Weijian Ye
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Yewei Huang
- College of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Congcong Sun
- College of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Youli Tao
- College of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Tao Wang
- College of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Weitao Cong
- College of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Funeng Geng
- Sichuan Key Laboratory of Medical American Cockroach, Chengdu, Sichuan 610000, P.R. China
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Liu J, Zhou L, He L, Zhong Y, Zhang X, Xiao B, Liu G. Periplaneta Americana Extract May Attenuate Renal Fibrosis through Inhibiting Janus Tyrosine Kinase 2/Signal Transducer and Activator of Transcription 3 Pathway. Pharmacology 2018; 102:1-8. [PMID: 29669350 DOI: 10.1159/000488535] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Accepted: 03/19/2018] [Indexed: 01/10/2023]
Abstract
BACKGROUND Periplaneta americana is one of the ancient insect groups with the strongest vitality. Periplaneta americana extract (PAE) has been explored as an alternative remedy for many diseases. Although much progress has been made in the study about PAE, the role of the drug in renal disease is rarely reported, especially in renal fibrosis. This study was designed to evaluate the renoprotective effect of PAE treatment to renal fibrosis. METHOD An in vivo, unilateral ureteral obstruction (UUO) mouse model was built. Then the mice were treated with PAE (100 mg/kg body weight) once daily by oral gavage, again starting on the day of UUO and continued for 1 week. At the end of 1 week, the mice were sacrificed; kidney samples were collected for further analysis. In vitro, Boston University mouse proximal tubular cells were plated in 35-mm dishes at a density of 0.3 * 106 cells/dish. Then the cells were treated with 5-ng/mL TGF-β1 in serum-free DMEM medium for an indicated length of time. The experimental groups were pretreated with the indicated concentrations of PAE (0.3125 mg/mL). The cells were further cultured for 24 h, and then cells were monitored morphologically or collected for biochemical analyses. RESULTS Both in vivo and vitro PAE inhibits the expression of FN and alpha-smooth muscle actin and suppresses renal fibrosis. Importantly, PAE protects against renal fibrosis by inhibiting Janus tyrosine kinase 2 (JAK)/signal transducer and activator of transcription 3 (STAT) tyrosine phosphorylation. CONCLUSION PAE attenuates renal fibrosis through the suppression of the JAK2/STAT3 pathway.
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Affiliation(s)
- Jingsong Liu
- Department of Nephrology, Hospital Affiliated to Hunan Academy of Chinese Medicine, Chinese Medicine and Western Medicine Hospital Affliated to Hunan University of Chinese Medicine, Changsha, China
| | - Lin Zhou
- Nephrology Department, The Second Xiangya Hospital, Central South University, Key Lab of Kidney Disease and Blood Purification in Hunan, Changsha, China
| | - Liyu He
- Nephrology Department, The Second Xiangya Hospital, Central South University, Key Lab of Kidney Disease and Blood Purification in Hunan, Changsha, China
| | - Ying Zhong
- Department of Nephrology, Hospital Affiliated to Hunan Academy of Chinese Medicine, Chinese Medicine and Western Medicine Hospital Affliated to Hunan University of Chinese Medicine, Changsha, China
| | - Xiaobai Zhang
- Department of Nephrology, Hospital Affiliated to Hunan Academy of Chinese Medicine, Chinese Medicine and Western Medicine Hospital Affliated to Hunan University of Chinese Medicine, Changsha, China
| | - Bofei Xiao
- Department of Nephrology, Hospital Affiliated to Hunan Academy of Chinese Medicine, Chinese Medicine and Western Medicine Hospital Affliated to Hunan University of Chinese Medicine, Changsha, China
| | - Guoyong Liu
- Department of Nephrology, The First Affiliated Hospital of Changde Vocational Technical College, Changde, China
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