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Chen X, Chen L, Chen B, Wei Q, Wu Y, Zhang Y. A Recombinant Lentiviral Vegfr2-Silencing Vector Attenuates Roxarsone-Promoted Growth of Rat Vascular Endothelial Cells and Angiogenesis in Matrigel Plug and B16F10 Xenograft Models. Vet Sci 2024; 11:451. [PMID: 39453043 PMCID: PMC11511396 DOI: 10.3390/vetsci11100451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 08/13/2024] [Accepted: 09/20/2024] [Indexed: 10/26/2024] Open
Abstract
Roxarsone (ROX) is widely used as a feed addictive for livestock and poultry. ROX promotes angiogenesis, which can lead to health problems, and it is necessary to identify methods to counter this angiogenic effect of ROX. The VEGF/VEGFR2 signaling pathway is involved in the growth and reconstruction of new blood vessels during angiogenesis. In this study, a recombinant lentiviral vector encoding Vegfr2 shRNA was transfected into rat vascular endothelial cells and used in mouse matrigel plug and melanoma xenograft models to investigate its potential to regulate ROX-induced angiogenesis and tumor growth. Treating endothelial cells with ROX increased cell proliferation, migration, and a tube-like structure of growth relative to the control group. The addition of the lentiviral Vegfr2-silencing vector significantly attenuated the effects of ROX on endothelial cells. The hemoglobin content of mouse matrigel plugs treated with ROX was increased significantly. This effect was dramatically attenuated by the co-administration of shRNA targeting Vegfr2. The volume, weight and CD34 staining of the melanoma xenograft tumors increased by ROX were also attenuated by Vegfr2 silence. These results indicate that the down-regulation of VEGFR2 protein plays an inhibitory role in the ROX-promoted angiogenesis in vivo and in vitro. These data support the targeting of Vegfr2 gene as an effective means to treat ROX-induced angiogenesis and tumor growth.
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Affiliation(s)
- Xin Chen
- Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; (X.C.)
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
| | - Lin Chen
- Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; (X.C.)
| | - Binlin Chen
- Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; (X.C.)
| | - Qianhan Wei
- Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; (X.C.)
| | - Yinchao Wu
- Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; (X.C.)
| | - Yumei Zhang
- Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; (X.C.)
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
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Li TT, Su XW, Chen LL, Zhang WN, Zhang JP, Wang Y, Xu WH. Roxarsone inhibits hepatic stellate cell activation and ameliorates liver fibrosis by blocking TGF-β1/Smad signaling pathway. Int Immunopharmacol 2023; 114:109527. [PMID: 36700762 DOI: 10.1016/j.intimp.2022.109527] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 11/04/2022] [Accepted: 11/28/2022] [Indexed: 12/23/2022]
Abstract
Hepatic fibrosis is a pathological change caused by chronic liver injury and self-repair, and it is the inevitable stage of the development of chronic liver disease to cirrhosis or even liver cancer. Activation of hepatic stellate cells (HSCs) is a core event in the development of liver fibrosis and blockage of the activation of HSCs has been shown to alleviate liver fibrosis. Roxarsone, an organoarsenic additive, with antibiotic effect, growth promotion and improving feed efficiency, is widely used in livestock and animal production. The purpose of this study was to evaluate the therapeutic effect of Roxarsone on liver fibrosis and explore the possible mechanism. We found that Roxarsone could inhibit transforming growth factor-β1 (TGF-β1) induced the activation of HSCs and weaken the migration ability. Moreover, Roxarsone administration significantly ameliorated CCl4-induced liver fibrosis in mice with improvement of liver function and decreases of deposition of extracellular matrix (ECM). Mechanism investigations revealed that Roxarsone specifically inhibited the activation of TGF-β1/Smad signaling pathway, but had no effect on MAPK and PI3K/AKT pathways. These results suggest that Roxarsone has a protective effect on liver fibrosis which provides a new candidate for the treatment of liver fibrosis.
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Affiliation(s)
- Ting-Ting Li
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China
| | - Xiao-Wei Su
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China
| | - Lin-Lin Chen
- College of Pharmacy, Second Military Medical University, Shanghai 200433, PR China
| | - Wan-Nian Zhang
- College of Pharmacy, Second Military Medical University, Shanghai 200433, PR China
| | - Jun-Ping Zhang
- College of Pharmacy, Second Military Medical University, Shanghai 200433, PR China; College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China
| | - Yan Wang
- College of Pharmacy, Second Military Medical University, Shanghai 200433, PR China.
| | - Wei-Heng Xu
- College of Pharmacy, Second Military Medical University, Shanghai 200433, PR China.
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Zhang M, Ding L, Zhou Z, Liu C, Wang C, Chen B, Chen X, Zhang Y. The VEGFR2/mTOR/S6K1 pathway involved in the angiogenic effects of roxarsone in vitro and in vivo. Toxicology 2022; 478:153290. [PMID: 35985552 DOI: 10.1016/j.tox.2022.153290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 08/11/2022] [Accepted: 08/11/2022] [Indexed: 11/26/2022]
Abstract
Roxarsone, an organoarsenic compound used in poultry industry to increase weight gain, is widely used as a feed additive in some developing countries. Roxarsone has a low absorption rate and is mostly excreted with feces, which could pose a risk to human health through environmental and animal food routes. Roxarsone has been demonstrated to have tumor-promoting and proangiogenic effects. Herein, we report the role of VEGFR2/mTOR/S6K1 signaling in roxarsone-promoted vessel endothelial cell growth and angiogenesis in the Matrigel plug model and the mouse B16 cell tumor transplantation model. In angiogenesis-related experiments in vitro, 1.0 μM roxarsone significantly increased the activity, proliferation, migration, and tube formation of rat vascular endothelial cells. In addition, 1.0 μM roxarsone upregulated the protein levels of mTOR, phosphorylated mTOR, S6K1, and phosphorylated S6K1 and significantly increase the expression of Mtor and S6k1 mRNA. Rapamycin and SU5416 significantly inhibited the effects of 1.0 μM roxarsone on cell growth. Furthermore, the weight, volume, and CD31 expression of B16-F10 xenografts and Matrigel plugs in mice were upregulated by 25 mg/kg roxarsone. The protein and mRNA levels of mTOR, S6K1 and its phosphorylated protein were significantly increased in the roxarsone treatment group in xenografts. SU5416 and a short hairpin RNA targeting Vegfr2 significantly reduced roxarsone-promoted xenograft and Matrigel plug growth. In summary, this study indicated that the VEGFR2/mTOR/S6K1 signaling plays a regulatory role in roxarsone-mediated promotion angiogenesis and enhanced tumor growth.
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Affiliation(s)
- Meng Zhang
- College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China
| | - Lijun Ding
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China; Jiangsu Agri-animal Husbandry Vocational College, Taizhou, Jiangsu 225300, China
| | - Zhiqiang Zhou
- College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China
| | - Chang Liu
- College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China
| | - Cunkai Wang
- College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China
| | - Binlin Chen
- College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China
| | - Xin Chen
- College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu 225009, China
| | - Yumei Zhang
- College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu 225009, China.
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Kennedy DC, Coen B, Wheatley AM, McCullagh KJA. Microvascular Experimentation in the Chick Chorioallantoic Membrane as a Model for Screening Angiogenic Agents including from Gene-Modified Cells. Int J Mol Sci 2021; 23:452. [PMID: 35008876 PMCID: PMC8745510 DOI: 10.3390/ijms23010452] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 12/29/2021] [Accepted: 12/29/2021] [Indexed: 02/07/2023] Open
Abstract
The chick chorioallantoic membrane (CAM) assay model of angiogenesis has been highlighted as a relatively quick, low cost and effective model for the study of pro-angiogenic and anti-angiogenic factors. The chick CAM is a highly vascularised extraembryonic membrane which functions for gas exchange, nutrient exchange and waste removal for the growing chick embryo. It is beneficial as it can function as a treatment screening tool, which bridges the gap between cell based in vitro studies and in vivo animal experimentation. In this review, we explore the benefits and drawbacks of the CAM assay to study microcirculation, by the investigation of each distinct stage of the CAM assay procedure, including cultivation techniques, treatment applications and methods of determining an angiogenic response using this assay. We detail the angiogenic effect of treatments, including drugs, metabolites, genes and cells used in conjunction with the CAM assay, while also highlighting the testing of genetically modified cells. We also present a detailed exploration of the advantages and limitations of different CAM analysis techniques, including visual assessment, histological and molecular analysis along with vascular casting methods and live blood flow observations.
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Affiliation(s)
| | | | - Antony M. Wheatley
- Department of Physiology, School of Medicine, Human Biology Building, National University of Ireland, H91 W5P7 Galway, Ireland; (D.C.K.); (B.C.)
| | - Karl J. A. McCullagh
- Department of Physiology, School of Medicine, Human Biology Building, National University of Ireland, H91 W5P7 Galway, Ireland; (D.C.K.); (B.C.)
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Chen X, Zhang M, Chen L, Zhou Z, Chen B, Wang C, Xie Y, Zhang Y. Roxarsone Promotes Glycolysis and Angiogenesis by Inducing Hypoxia-Inducible Factor-1α In Vitro and In Vivo. ACS OMEGA 2021; 6:9559-9566. [PMID: 33869936 PMCID: PMC8047655 DOI: 10.1021/acsomega.1c00072] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 03/18/2021] [Indexed: 06/12/2023]
Abstract
Roxarsone (Rox) is an organic arsenic compound used as a feed additive to promote animal growth. The release of Rox into the environment poses risks to human health. Rox demonstrated tumor-promoting and proangiogenic effects in xenograft models. Increasing studies revealed the tight relationship among angiogenesis, carcinogenesis, tumorigenesis, and glycolysis. Glycolysis, via hypoxia-inducible factor-1α (HIF-1α), controls vascular endothelial cell (VEC) growth. To date, there has been no literature report on the effect of Rox on HIF-1α-dependent glycolysis. Herein, we report that Rox promoted glycolysis in rat VECs, as shown by the increased adenosine triphosphate production, the lactic acid release, the activity and content of aldolase (ALD), and the expression levels of ALD A and glucose transporter 1 (GLUT1). Rox also increased the cellular levels of HIF-1α. Treatment with the HIF-1α inhibitor YC-1 reversed Rox-increased ALD A and GLUT1 levels and attenuated Rox-induced VEC viability, suggesting that Rox-induced HIF-1α contributes to the glycolytic and angiogenic effects of Rox. Rox also promoted tumor growth and angiogenesis and increased the levels of ALD A, GLUT1, and HIF-1α in the tumor tissue of a mouse xenograft model, whereas these effects were abolished using YC-1. Our findings indicated that Rox induces HIF-1α in VECs to promote glycolysis and angiogenesis thus enhancing the tumor growth.
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Affiliation(s)
- Xin Chen
- Department
of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009 Jiangsu, China
- Jiangsu
Co-innovation Center for Prevention and Control of Important Animal
Infectious Diseases and Zoonoses, Yangzhou, 225009 Jiangsu, China
- Joint
International Research Laboratory of Agriculture and Agri-Product
Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, 225009 Jiangsu, China
| | - Meng Zhang
- Department
of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009 Jiangsu, China
| | - Linzhongri Chen
- Department
of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009 Jiangsu, China
| | - Zhiqiang Zhou
- Department
of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009 Jiangsu, China
| | - Binlin Chen
- Department
of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009 Jiangsu, China
| | - Cunkai Wang
- Department
of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009 Jiangsu, China
| | - Yang Xie
- Department
of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009 Jiangsu, China
| | - Yumei Zhang
- Department
of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009 Jiangsu, China
- Jiangsu
Co-innovation Center for Prevention and Control of Important Animal
Infectious Diseases and Zoonoses, Yangzhou, 225009 Jiangsu, China
- Joint
International Research Laboratory of Agriculture and Agri-Product
Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, 225009 Jiangsu, China
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VEGF/Flk1 Mechanism is Involved in Roxarsone Promotion of Rat Endothelial Cell Growth and B16F10 Xenograft Tumor Angiogenesis. Sci Rep 2019; 9:17417. [PMID: 31758020 PMCID: PMC6874592 DOI: 10.1038/s41598-019-53870-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Accepted: 11/06/2019] [Indexed: 01/08/2023] Open
Abstract
The potential angiogenic effect of roxarsone, a feed additive widely used to promote animal growth worldwide, was demonstrated recently. We explored the mechanism of vascular endothelial growth factor (VEGF) and its receptor (VEGFR) in roxarsone promotion of rat vascular endothelial cells (ECs) and B16F10 mouse xenografts. ECs were treated with 0.1–50 μM roxarsone or with roxarsone plus 10 ng/mL VEGF, VEGFR1 (Flt1), or VEGFR2 (Flk1) antibodies for 12–48 h to examine their role in cell growth promotion. Small interfering RNA (siRNA) targeting Vegf, Flt1, and Flk1 were transfected in the ECs, and we measured the expression level, cell proliferation, migration, and tube formation ability. The siRNA targeting Vegf or Flk1 were injected intratumorally in the B16F10 xenografts of mice that received 25 mg/kg roxarsone orally. Cell viability and VEGF expression following roxarsone treatment were significantly higher than that of the control (P < 0.05), peaking following treatment with 1.0 μM roxarsone. Compared to roxarsone alone, the VEGF antibody decreased cell promotion by roxarsone (P < 0.05), and the Flk1 antibody greatly reduced cell viability compared to the Flt1 antibody (P < 0.01). Roxarsone and Flk1 antibody co-treatment increased supernatant VEGF significantly, while cellular VEGF was obviously decreased (P < 0.01), whereas there was no significant difference following Flt1 antibody blockade. The siRNA against Vegf or Flk1 significantly attenuated the roxarsone promotion effects on EC proliferation, migration, and tube-like formation (P < 0.01), whereas the siRNA against Flt1 effected no obvious differences. Furthermore, the RNA interference significantly weakened the roxarsone-induced increase in xenograft weight and volume, and VEGF and Flk1 expression. Roxarsone promotion of rat EC growth, migration, and tube-like formation in vitro and of B16F10 mouse xenograft model tumor growth and angiogenesis involves a VEGF/Flk1 mechanism.
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Pang Y, Wang K, Wang Y, Chenlin Z, Lei W, Zhang Y. Tumor-promoting and pro-angiogenic effects of roxarsone via VEGFR2/PLCγ/PKC signaling. Chem Biol Interact 2018; 292:110-120. [PMID: 30028964 DOI: 10.1016/j.cbi.2018.07.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Revised: 07/01/2018] [Accepted: 07/16/2018] [Indexed: 01/21/2023]
Abstract
Roxarsone is an organoarsenic feed additive used in livestock and poultry production that is released into the environment, where it poses a risk to human health. It is known to have a tumor-promoting effect that is brought about by pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and it receptors (VEGFR). However, little information is available about the other signaling molecules that could be involved. This study aims to investigate the role of PLCγ/PKC signaling in roxarsone-induced angiogenesis in a mouse B16-F10 melanoma xenograft model and rat vascular endothelial cells (ECs). Results showed treatment with 5 mg/kg and 25 mg/kg roxarsone resulted in an obvious increase in the weight and volume of B16-F10 xenografts and PLCγ/PKC phosphorylation in a dose-dependent manner in C57BL/6 mice. SU5416, a VEGFR2 inhibitor, significantly attenuated the tumor growth induced by roxarsone. Further, 1.0 μmol/L roxarsone treatment in rat ECs was observed to significantly increase the optical density rate in the MTT assay, the number of BrdU-positive cells in the proliferation assay, the migration distance in the scratch test, and the number of meshes formed in the tube formation assay. In addition, treatment with 1.0 μmol/L roxarsone was associated with significantly higher phosphorylation of PLCγ/PKC than the control treatment. U73122, a PLCγ inhibitor, was found significantly to combat the effects of 1.0 μmol/L roxarsone on the ECs. Roxarsone is capable of promoting the growth of mouse B16-F10 xenografts and tube formation in vascular ECs. Moreover, VEGFR2/PLCγ/PKC signaling may play a regulatory role in in vivo and in vitro roxarsone-induced angiogenesis.
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Affiliation(s)
- Yanhua Pang
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, PR China.
| | - Kai Wang
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, PR China.
| | - Yujing Wang
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, PR China
| | - Zhongri Chenlin
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, PR China
| | - Weiwei Lei
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, PR China
| | - Yumei Zhang
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious, Diseases and Zoonoses, Yangzhou, PR China.
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Chen Y, Tian JL, Wu JS, Sun TM, Zhou LN, Song SJ, You S. Biotransfomation of cyperenoic acid by Cunninghamella elegans AS 3.2028 and the potent anti-angiogenic activities of its metabolites. Fitoterapia 2017; 118:32-37. [DOI: 10.1016/j.fitote.2017.02.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Revised: 02/12/2017] [Accepted: 02/14/2017] [Indexed: 10/20/2022]
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Wang Y, Yin D, Xu C, Wang K, Zheng L, Zhang Y. Roxarsone induces angiogenesis via PI3K/Akt signaling. Cell Biosci 2016; 6:54. [PMID: 27708768 PMCID: PMC5039879 DOI: 10.1186/s13578-016-0119-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Accepted: 09/20/2016] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND 3-Nitro-4-hydroxy phenyl arsenic acid, roxarsone, is widely used as an organic arsenic feed additive for livestock and poultry, which may increase the level of arsenic in the environment and the risk of exposure to arsenic in human. Little information is focused on the angiogenesis roxarsone-induced and its mechanism at present. This paper aims to study the role of PI3K/Akt signaling in roxarsone-induced angiogenesis in rat vascular endothelial cells and a mouse B16-F10 melanoma xenograft model. RESULTS The results showed that treatment with 0.1-10.0 µmol/L roxarsone resulted in an increase in the OD rate in the MTT assay, the number of BrdU-positive cells in the proliferation assay, the migration distance in the scratch test and the number of meshes in tube formation assay. Further, treatment with 1.0 µmol/L roxarsone was associated with significantly higher phosphorylation of PI3K/Akt and expression of VEGF than the control treatment. The PI3K inhibitor was found to significantly combat the effects of 1.0 µmol/L roxarsone. Furthermore, roxarsone treatment was observed to increase the weight and volume of B16-F10 xenografts and VEGF expression and PI3K/Akt phosphorylation in a dose-dependent manner, with the 25 mg/kg dose having significant effects. CONCLUSIONS These results demonstrate that roxarsone has the ability to promote growth and tube formation in vascular endothelial cells and the growth of mouse B16-F10 xenografts. Further, the findings also indicate that PI3K/Akt signaling plays a regulatory role in roxarsone-induced angiogenesis in vivo and in vitro.
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Affiliation(s)
- Yujing Wang
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, 12# Wenhui East Road, Yangzhou, 225009 Jiangsu China
| | - Donglai Yin
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, 12# Wenhui East Road, Yangzhou, 225009 Jiangsu China
| | - Chao Xu
- Department of Veterinary Internal Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu China
| | - Kai Wang
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, 12# Wenhui East Road, Yangzhou, 225009 Jiangsu China
| | - Lingmin Zheng
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, 12# Wenhui East Road, Yangzhou, 225009 Jiangsu China
| | - Yumei Zhang
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, 12# Wenhui East Road, Yangzhou, 225009 Jiangsu China
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
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