Celastrus Orbiculatus Extracts Inhibit the Metastasis through Attenuating PI3K/Akt/mTOR Signaling Pathway in Human Gastric Cance.

BACKGROUND: Rapamycin receptor inhibitors have been applied in clinic and have achieved satisfactory therapeutic effect recently. The mechanisms have not clearly underlying the Celastrus orbiculatus Extracts (COE) inhibited the expression of the mammalian Target of Rapamycin (mTOR) in human gastric cancer cells. The aim of this study was to investigate whether the COE inhibited the metastasis through mTOR signaling pathway in human gastric cancer MGC-803 cells. METHODS: The abnormal expression level of mTOR protein was detected by immunohistochemistry in human gastric cancer tissue. The MGC-803/mTOR- cells were constructed by knockdown of mTOR using lentivirus infection technique. The human gastric cancer MGC-803/mTOR- cells were treated with different concentrations (20, 40, 80 μg/ml) of COE for 24 hours. The ability of cell metastasis was analyzed by the cell invasion and migration assay. The expression levels of PI3K/Akt/mTOR signaling pathway were detected by Western Blotting. RESULTS: COE inhibited the proliferation, invasion and migration of MGC-803/mTOR- cells in a concentration dependent manner. The expression of E-cadherin protein was increased, and the expression of N-cadherin and Vimentin were decreased simultaneously in the MGC-803/mTOR- cells. 4EBP1, p-4EBP1, P70S6k, p-P70S6k, mTOR, p-mTOR, PI3K and Akt proteins in MGC-803/mTOR- cells were reduced in dose-dependent manners. CONCLUSION: COE could not only inhibit cell growth, invasion and migration, but also inhibit the epithelial-mesenchymal transition of gastric cancer cells. The molecular mechanism of COE inhibited the metastasis may be related to the PI3K/Akt/mTOR signal pathway. This study provides ideas for the development of new anti-gastric cancer drugs.