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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。
Objective: To investigate the effect and mechanism of homoharringtonine (HHT) combined with survivin inhibitor YM155 on proliferation and apoptosis induction in human leukemia K562 cell line. Methods: The inhibitory rate of cell proliferation was detected by CCK method. The combination therapy of HHT and YM155 was evaluated according to the principle of moderate effect and CalcuSyn software. The control group, HHT group, YM155 group and combination group were established. The apoptosis rate was detected by flow cytometry with Annexin V / PI double staining method. The expression of survivin protein was detected by Western blot. The caspase -3, -8 activity changes. Results: Both HHT and YM155 alone inhibited the growth of K562 cells in a concentration-dependent manner. The combination of the two showed chemotherapeutic synergistic effects (CI <1). The apoptosis rate of K562 cells in the combination group was significantly higher than that in the untreated group, and the expression of survivin protein was significantly down-regulated (all P <0.05). HHT monotherapy and combination therapy induced caspase-3, -8 activation, while YM155 alone did not cause changes in caspase-3, -8 activity. Conclusion: The combination of HHT and YM155 has a synergistic effect on chemotherapy of K562 cells and down-regulates the apoptosis of K562 cells by survivin.