Xiaopu He1, Mengxue Sun2, Peiyun Huang1, Shuaishuai Zhuang1, Weihao Sun1*, Jie Hua3*
Cyclooxygenase-2 (COX-2) plays an important role in the carcinogenesis and progression of gastric cancer. Z-guggulsterone has been used as an antibacterial and anticancer agent; however, effects and action mechanism of Z-guggulsterone on the human gastric cancer cells remain unclear. This study evaluated the antitumor effects of Z-guggulsterone on human gastric cancer both in vitro and in vivo . Our results showed that Z-guggulsterone significantly inhibited cellular proliferation, migration and induced apoptosis in vitro, as well as inhibited tumor growth in vivo. In addition, Z-guggulsterone significantly inhibited the expression of Bcl-2, p-Akt and COX-2 as well as increased Bax and PTEN expression in gastric cancer cells. The PTEN inhibitor reversed Z-guggulsterone -induced down regulation of p-Akt and COX-2 expression. The Akt inhibitor combined with Z-guggulsterone can downregulate the expression levels of p-Akt and COX-2, and the combined effect was better than that of Z-guggulsterone alone. These results collectively indicate that Z-guggulsterone inhibits proliferation and induces apoptosis of gastric cancer cells may be mediated by down-regulation of COX-2 expression through PTEN/Akt signaling pathway.