YM155 enhances apoptosis in triple negative breast cancer MDA-MB-231 cells via autophagy
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    Abstract:

    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,beclin 1 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 and LC-3 were detected by Western blot. Results:It was revealed that YM155 significantly inhibited the growth of MDA-MB-231 cells in a dose-and time-dependent model. The apoptosis rates of cells treated with 0.5,1.0,1.5 ng/mL YM155 were (11.9 ± 2.4)%,(21.7 ± 2.6)%,and (30.8 ± 4.5)%,respectively,which all had significant difference compared to control cells[(6.4 ± 1.2)%]. When a combination of 3-MA effect after 24 h,cell proliferation rate was significantly enhanced compared to that of 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 caspase-3,PARP,beclin1 and LC-3 were increased. Compared with the YM155 group,the protein levels of LC-3 and caspase-3 were lower in YM155 + 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.

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樊晓东,甄林林,刘敏敏,厉 芝,宋 玮,丁亦含,施建华. YM155诱导乳腺癌细胞MDA-MB-231自噬并促进其凋亡[J].南京医科大学学报(自然科学版英文版),2015,(12):1697-1702.

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  • Received:March 27,2015
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  • Online: January 04,2016
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