Celastrus orbiculatus extracts inhibit invasion and metastasis in human hepatocellular carcinoma HepG2 cells by targeting mTOR / 中草药

ABSTRACT

Objective To investigate the molecular mechanisms of Celastrus orbiculatus extracts (COE) of the invasion and metastasis inhibition in human hepatocellular carcinoma HepG2 cells by targeting mTOR. Methods The HepG2/mTOR- cells with mTOR knockout expression were constructed by using siRNA technology. The effect of COE on the proliferation of the HepG2/mTOR- cells was also studied. The HepG2/mTOR- cells were treated with COE in different concentrations (20, 40, 80, 160, and 320 mg/L) for 24 h. The cell reproductive capability of HepG2/mTOR- cells was detected by MTT. The effect of COE on the metastatic ability of HepG2/mTOR- cells in vitro was investigated by scratch assay and Transwell migration assay. The expression levels of molecular mechanisms related proteins MMP-2 and MMP-9 were assessed by Western blotting. Results The HepG2/mTOR- cells with mTOR knockout expression were successfully constructed. COE significantly inhibited the proliferation of HepG2/mTOR- cells in a concentration-dependent manner (P < 0.05). COE decreased the invasion and migration of HepG2/mTOR- cells. The results of Transwell experiment indicated that COE (80 mg/L) significantly reduced the number of transmembrane cells (P < 0.05). And the expression levels of MMP2 and MMP9 protein were significantly reduced in the HepG2/mTOR- cells after the treatment of COE. Conclusion COE can significantly inhibit the proliferation, invasion, and migration in the HepG2/mTOR- cells. Our data reveal that COE is a potential chemotherapeutic drug in human hepatocellular carcinoma treatments via targeting mTOR signal pathway.