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
Abstract
BACKGROUND

Gastric cancer is one of the most common malignant tumors of the digestive system worldwide, posing a serious danger to human health. Cyclooxygenase (COX)-2 plays an important role in the carcinogenesis and progression of gastric cancer. Acetyl-11-keto-β-boswellic acid (AKBA) is a promising drug for cancer therapy, but its effects and mechanism of action on human gastric cancer remain unclear.

AIM

To evaluate whether the phosphatase and tensin homolog (PTEN)/Akt/COX-2 signaling pathway is involved in the anti-tumor effect of AKBA in gastric cancer.

METHODS

Human poorly differentiated BGC823 and moderately differentiated SGC7901 gastric cancer cells were routinely cultured in Roswell Park Memorial Institute 1640 medium supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin. Gastric cancer cell proliferation was determined by methyl thiazolyl tetrazolium colorimetric assay. Apoptosis was measured by flow cytometry. Cell migration was assessed using the wound-healing assay. Expression of Bcl-2, Bax, proliferating cell nuclear antigen, PTEN, p-Akt, and COX-2 were 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.

RESULTS

AKBA significantly inhibited the proliferation of gastric cancer cells in a dose- and time-dependent manner, inhibited migration in a time-dependent manner, and induced apoptosis in a dose-dependent manner in vitro; it also inhibited tumor growth in vivo. AKBA up-regulated the expression of PTEN and Bax, and down-regulated the expression of proliferating cell nuclear antigen, Bcl-2, p-Akt, and COX-2 in a dose-dependent manner. The PTEN inhibitor bpv (Hopic) reversed the high expression of PTEN and low expression of p-Akt and COX-2 that were induced by AKBA. The Akt inhibitor MK2206 combined with AKBA down- regulated the expression of p-Akt and COX-2, and the combined effect was better than that of AKBA alone.

CONCLUSION

AKBA inhibits the proliferation and migration and promotes the apoptosis of gastric cancer cells through the PTEN/Akt/COX-2 signaling pathway.

Keywords: Acetyl-11-keto-β-boswellic acid, Gastric cancer, Cell proliferation, Apoptosis, Cyclooxygenase-2, Tumor xenograft

Core tip: Cyclooxygenase-2 is involved in the carcinogenesis and development of gastric cancer, and is closely related to its prognosis. Acetyl-11-keto-β-boswellic acid is a promising drug for gastric cancer therapy. It inhibits the proliferation and induces the apoptosis of gastric cancer cells, possibly via mechanisms associated with down-regulation of cyclooxygenase-2 expression through the phosphatase and tensin homolog/Akt signaling pathway.