Effects of YM155 on proliferation and apoptosis of triple negative breast cancer MDA-MB-231 cells

Objective To investigate the apoptosis induction effects and the possible mechanism of YM155 on triple negative breast cancer MDA-MB-231cells. Methods MDA-MB-231 cells were treated with different concentrations of YM155, and the survival rate of the cells was determined by CCK-8 assay and the half maximal inhibitory concentration(IC50)value of YM155 was calculated. The apoptosis rate was examined by Annexin V-FITC/PI double staining. mRNA expression of survivin and bcl-2 in MDA-MB-231cells was detected by RT-PCR. The protein expression of survivin, bcl-2, caspase-3, and PARP were detected by Western blot. Results YM155 significantly inhibited the growth of MDA-MB-231 cells in a dose-and-time-dependenct way. IC50 was(1.749±0.265)ng/ml and(0.823±0.125)ng/ml respectively at 24 and 48 hours. The apoptosis rate of cells treated with 0.5 ng/ml, 1.0 ng/ml, and 1.5 ng/ml YM155 was (10.93±0.94)%, (31.10±1.51)%, and(46.83±2.92)% respectively, which had significant difference compared to that of the control group(6.4±1.2)%(P<0.01). YM155 could significantly decrease mRNA and protein expression of surviving, besides, it reduced bcl-2 expression and increased caspase-3 and PARP protein expression. Conclusions YM155 can effectively induce the apoptosis of MDA-MB-231 cells by downregulating survivin and activating caspase pathway. Bcl-2 might play a role in the apoptosis. Key words: YM155; Triple negative breast cancer; Survivin; Apoptosis