Effects Of YM155 On Proliferation And Apoptosis Of Triple Negative Breast Cancer MDA-MB-231 Cells

Objective:To investigate the effect of YM155, a survivin inhibitor, on the apoptosis and autophagy of the triple negative breast cancer MDA-MB-231 cells.Methods:MDA-MB-231 cells was treated with different concentrations of YM155,the survival rate of the cells was determined by CCK-8 assay and the IC50(half inhibitory concentration) value of YM155 was calculated. The apoptosis rate was examined by Annexin V-FITC/PI double staining. The mRNA expression of survivin and bcl-2 in MDA-MB-231 cells was detected by Real-time PCR.The protein expression of survivin,bcl-2,caspase 3,PARP,beclin 1,LC-3 were detected by Western blot.Results:It was revealed that YM155 could significantly inhibit the growth of MDA-MB-231 cells under the dose and time dependency. The apoptosis rates of cells treated with 0.5、1.0、1.5ng/ml YM155 were 11.9±2.4%、21.7±2.6%、 30.8±4.5%,respectively, which all had significant difference to control cells (6.4±1.2%).When a combination of 3-MA effect after 24h, cell proliferation rate was significantly enhanced than the single YM155 group (P<0.05).With the increasing of YM155 concentration, the expression levels of mRNA and protein of survivin and BCL-2 were decreased, while the expression levels of cleaved caspase-3, PARP, beclinl and LC-3 were increased. Compared with the YM155 group, the protein levels of LC-3 and caspase-3 were lower in YM155 united 3-MA group.Conclusion:YM155 could effectively inhibit MDA-MB-231 cells proliferation by inducing apoptosis and autophagy, while autophagy induction effect can enhance its apoptosis effect.