Role of tangeretin on autophagy in human gastric cancer AGS cells and its mechanism / 中国药理学通报

ABSTRACT

Aim To investigate the effect of tangeretin on autophagy of human gastric cancer AGS cells and its molecular mechanisms. Methods Western blot was used to detect the effect of tangeretin on expression of LC3, p62 and Akt phosphorylation, and the effects of autophagy inhibitor CQ and activator Rapa on tangere-tin-regulated autophagy. Annexin V/PI double staining was used to quantitatively detect the effect of CQ on apoptosis of cells induced by iangeretin. Results 24h after treatment, tangeretin enhanced the expression of LC3 II protein (P < 0. 05 , P < 0. 01) and p62 (P < 0. 05) in a dose-dependent manner. 48 h after treatment, tangeretin enhanced the expression of p62 protein in a dose-dependent manner (P < 0. 05, P < 0. 01) , and had no significant effect on expression of LC3II protein. At 24 h and 48 h, the expression of LC3II and p62 increased significantly in CQ + Tan group compared with that of Tan group (P < 0. 01). Compared with Tan group, the expression of LC3II and p62 protein decreased in Rapa + Tan group, and there was a statistical difference (P < 0. 05). The apoptotic rate of AGS cells in CQ + Tan group was significantly higher than that in Tan group (P <0. 01). The phosphorylation levels of Akt protein were reduced by tan-gerin for 24 and 48 h in a dose-dependent manner (P <0. 05 , P < 0. 01). Conclusions Tangeretin may promote cell apoptosis by inhibiting the autophagic flux in human gastric cancer AGS cells. Akt phosphorylation might be involved in the autophagy and apoptosis.