Survivin inhibitor YM155 inhibits proliferation of hepatocellular carcinoma cells by inducing autophagy

Abstract

Objective To investigate the effects of YM155, a small molecule Survivin inhibitor, on the proliferation of hepatocellular carcinoma (HCC) cells and to explore its molecular mechanism. Methods After HCC cell line SK-Hep-1 was treated with different concentrations of YM155 (0-60 nmol/L), cell proliferation rate of 24, 48 h was assessed by methyl thiazol tetrazolium (MTT), dead cells of 60 h were examined by trypan blue exclusion. SK-Hep-1 cells were treated with 20 nmol/L YM155 for 12 h and 24 h, the expression of Beclin 1, LC3 Ⅰ/Ⅱ, B cell lymphoma/leukemia-2 (bcl-2) and myeloid cell leukemia-1 (Mcl-1) were detected by Western blotting. Results MTT showed that YM155 (0-60 nmol/L)inhibit the proliferation of HCC cells in time and concentration-dependent manner. After treatment with 2 nmol/L and 4 nmol/L YM155 for 60 h, trypan blue exclusion assay showed, dead cells rates were 45% and 90% respectively (P=0.025) relative to the control group [dimethylsurfoxide (DMSO)]; Western blotting results showed that, after SK-Hep-1 cells were treated with 20 nmol/L YM155 for 12 h and 24 h, Beclin 1 and LC3 Ⅱ protein expression levels were increased, while Mcl-1 expession was downregulated, but bcl-2 expression was not altered. Conclusion YM155 significantly suppresses HCC cell proliferation and induced autophagy. Anti-cancer activities of YM155 may be associated with downregulation of Mcl-1 and induction of autophagic cell death. Key words: YM155; Hepatocellular carcinoma; Autophagy; Myeloid cell leukemia-1 gene