The study on YM155-sensitized lexatumumab-induced apoptosis in hepatocellular carcinoma cells

ZHAO Xiangxuan; WEN Feng; REN Ying; SUN Wei; LIANG Hongyuan; ZHAO Gang; LU Zaiming

Abstract：Objective To investigate the roles of small molecule compound YM155 in lexatumumab-induced apoptosis in hepatocellular carcinoma(HCC) LH86 cells and the possible mechanism. Methods HCC LH86 cells were cultured in vitro. Control group(DSMO), YM155-treated group(1 μmol/ L), lexatumumab-treated group(1 μg/ ml) and YM155 plus lexatumumab-treated group(1 μmol/ L YM155+1 μg/ ml lexatumumab) were set up. Cells untreated or treated with various conditions were observed under microscope to show necleus fragmentation and calculate cell apoptotic rate. Western blotting was performed to detect apoptotic marker molecule caspase-3 cleavage activation and Bax conformational activation. Results YM155(1 μmol/ L) and lexatumumab(1 μg/ ml) did not induce nucleus fragmentation in LH86 cells. Interestingly, 1 μmol/ L YM155 significantly sensitized lexatumumab-induced ap-optosis in HL86 cells. The apoptotic rate of YM155 plus lexatumumab-treated group was 60%,higher than the other 3 groups( P<0. 05). The combination treatment effectively increased cleaved caspase-3 protein levels. Mechanism analysis revealed that YM155 and lexatumumab could promote Bax activation through its conformational change. Conclusion YM155 is able to sensitize monoclonal anti-body lexatumumab-induced apoptosis in HCC cells,which may be mediated by Bax conformational activation.