Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2020; 26(38): 5822-5835
Published online Oct 14, 2020. doi: 10.3748/wjg.v26.i38.5822
Acetyl-11-keto-β-boswellic acid inhibits proliferation and induces apoptosis of gastric cancer cells through the phosphatase and tensin homolog /Akt/ cyclooxygenase-2 signaling pathway
Meng-Xue Sun, Xiao-Pu He, Pei-Yun Huang, Qi Qi, Wei-Hao Sun, Gao-Shuang Liu, Jie Hua
Meng-Xue Sun, Xiao-Pu He, Pei-Yun Huang, Wei-Hao Sun, Gao-Shuang Liu, Department of Geriatric Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu Province, China
Qi Qi, Nanjing Medical University, Nanjing 210000, Jiangsu Province, China
Jie Hua, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu Province, China
Author contributions: Sun MX and He XP contributed equally to this work; Sun MX, He XP, Huang PY, Sun WH, and Hua J designed the research study; Sun MX, He XP, Huang PY, and Qi Q completed in vivo and in vitro experiments for this study; Sun WH, Hua J, and Liu GS contributed new reagents and analytic tools; Sun MX, He XP, and Hua J analyzed the data and wrote the manuscript; all authors have read and approved the final manuscript.
Supported by the Natural Science Foundation of Jiangsu, No. BK20171508
Institutional animal care and use committee statement: The study was reviewed and approved by the Animal Ethical and Welfare Committee of Nanjing Medical University.
Conflict-of-interest statement: The authors have no conflict to disclose.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at huajie@njmu.edu.cn. Participants gave informed consent for data sharing.
ARRIVE guidelines statement: The manuscript has been revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Jie Hua, Assistant Statistician, Doctor, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210000, Jiangsu Province, China. huajie@njmu.edu.cn
Received: May 26, 2020
Peer-review started: May 26, 2020
First decision: July 29, 2020
Revised: August 8, 2020
Accepted: August 26, 2020
Article in press: August 26, 2020
Published online: October 14, 2020
ARTICLE HIGHLIGHTS
Research background

Gastric cancer is a digestive malignancy with high incidence and mortality globally. Despite therapeutic improvement, it remains a leading cause of cancer-associated deaths. Gastric cancer can be diagnosed early by endoscopy and treated by timely surgical excision, but the patient’s long-term survival is still threatened by high metastasis, recurrence, and drug resistance. Active medicinal compounds from natural sources have provided alternative treatment options.

Research motivation

Gastric cancer is a global health threat. Cyclooxygenase (COX)-2 plays an important role in the carcinogenesis and progression of gastric cancer. The effects of acetyl-11-keto-β-boswellic acid (AKBA) on human gastric cancer remain unclear.

Research objectives

The objective of this study was to evaluate the anti-tumor effects and mechanisms of AKBA in human gastric cancer both in vitro and in vivo.

Research methods

Human gastric cancer cell lines BGC823 and SGC7901 were routinely cultured in RPMI-1640 medium supplemented with 10% heat-inactivated fetal calf serum. Sub-confluent cell cultures were treated with AKBA at a final concentration of 10-50 μM for 24, 48, and 72 h, and the cell proliferation was determined using methyl thiazolyl tetrazolium colorimetric assay. Apoptosis was assessed via flow cytometry analysis. The wound healing assay was performed to evaluate the effects of AKBA on the migration of gastric cancer cells. The expression of proliferating cell nuclear antigen (PCNA), COX-2, Bcl-2, Bax, phosphatase and tensin homolog (PTEN), Akt, and phosphorylated Akt was detected by Western blot analysis. A xenograft nude mouse model of human gastric cancer was established to evaluate the anti-cancer effect of AKBA in vivo.

Research results

AKBA significantly inhibited cellular proliferation and migration and induced apoptosis in vitro, as well as inhibited tumor growth in vivo. Additionally, AKBA significantly inhibited the expression of PCNA, COX-2, Bcl-2, and phosphorylated Akt as well as increased PTEN and Bax expression in gastric cancer cells.

Research conclusions

AKBA could prevent the development of gastric cancer through the PTEN/Akt/COX-2 signaling pathway.

Research perspectives

COX-2 is involved in the carcinogenesis and development of gastric cancer. AKBA is a promising drug for gastric cancer therapy.