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.

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.

• Authors: Meng-Xue Sun, Xiao-Pu He, Pei-Yun Huang, Qi Qi, Wei-Hao Sun, Gao-Shuang Liu, Jie Hua
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 26 Issue 38 Pg. 5822-5835 (Oct 14 2020) ISSN: 2219-2840 [Electronic] United States
• PMID: 33132637 (Publication Type: Journal Article)
• Copyright: ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.

Chemical References

• Tensins
• Triterpenes
• acetyl-11-ketoboswellic acid
• Cyclooxygenase 2
• Proto-Oncogene Proteins c-akt
• Phosphoric Monoester Hydrolases
• PTEN Phosphohydrolase

Topics

• Animals
• Apoptosis
• Cell Line, Tumor
• Cell Proliferation
• Cyclooxygenase 2
• Humans
• Mice
• Mice, Nude
• PTEN Phosphohydrolase
• Phosphoric Monoester Hydrolases
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction
• Stomach Neoplasms (drug therapy)
• Tensins
• Triterpenes (pharmacology)
• Xenograft Model Antitumor Assays