Acetyl-11-keto-ß-boswellic acid inhibits proliferation and induces apoptosis of gastric cancer cells through the phosphatase and tensin homolog /Akt/ cyclooxygenase-2 signaling pathway.
World J Gastroenterol
; 26(38): 5822-5835, 2020 Oct 14.
Article
em En
| MEDLINE
| ID: mdl-33132637
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-ß-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.Palavras-chave
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
/
Triterpenos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article