Effects of homharringtonine plus survivin inhibitor YM155 on the proliferation and apoptosis of human leukemia cell line K562
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摘要: 目的:探讨高三尖杉酯碱(HHT)联合survivin抑制剂YM155对人白血病K562细胞系增殖抑制和诱导凋亡的作用及机制。方法:CCK法检测细胞增殖抑制率,依据中效原理及CalcuSyn软件评价HHT和YM155的联合治疗效果。设空白对照组、HHT组、YM155组和联合用药组,采用Annexin V/PI双染法以流式细胞仪检测细胞凋亡率,Western blot法检测survivin蛋白变化,以特异性荧光底物检测caspase-3、-8活性变化。结果:HHT和YM155单药均以浓度依赖方式抑制K562细胞生长,二者联合应用具有化疗协同作用(CI<1)。联合用药组K562细胞凋亡率明显高于单独用药组,且survivin蛋白表达显著下调(均P<0.05)。HHT单药及联合用药组诱导caspase-3、-8活化,而YM155单药未引起caspase-3、-8活性变化。结论:HHT和YM155联合应用于K562细胞具有化疗协同作用,通过下调survivin诱导K562细胞凋亡。Abstract: Objective:To explore the combination applications of homharringtonine (HHT) and the survivin inhibitor YM155 on the proliferation and apoptosis of human leukemia cell line K562 and its mechanism.Methods:CCK-8 assay was used to determine the growth inhibition.The combination index CI of HHT and YM155 was calculated using the Chou-talalay methods by CalcuSyn software.The cells were divided into 4 groups:control group,HHT group,YM155 group,and combination group.The cell apoptosis rates were evaluated by flow cytometry.The expressions of associated proteins were detected by Western blot.Caspase-3 and -8 activities were determined using the specific fluorogenic substrates.Results:The inhibitory rates on cell growth by HHT and YM155 alone increased in concertration-dependent manner.The application of HHT and YM155 had synergistic effect (CI<1).The apoptosis rate was higher in combination group than those of one drug group and the protein expression levels of survivin decreased remarkably in combination group (P<0.05).Caspase-3 and -8 were activated by HHT or combination treatment,but not by YM155. Conclusion:The combination treatment with HHT and YM155 on K562 cells has synergistic effect.The mechanism is related to the apoptosis induced through down-regulation of survivin.
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Key words:
- homharringtonine /
- YM155 /
- K562cells
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