高三尖杉酯碱联合伊马替尼对K562/G01细胞的作用及机制研究

Effect of Homoharringtonine Combined with Imatinib on the K562/G01 Cells and Its Mechanism

目的:探索高三尖杉酯碱(Homoharringtonine,HHT)联合伊马替尼(Imatinib,IM)对K562/G01细胞增殖、凋亡的影响及其可能的作用机制。方法:应用CCK-8法检测HHT联合IM对K562/G01细胞增殖的影响,流式细胞术检测细胞的凋亡率及磷酸化酪氨酸水平,Western blot检测P210及PI3K/Akt信号通路相关蛋白的表达水平。结果:HHT联合IM与单药相比,对K562/G01细胞的增殖活性具有明显抑制作用(P<0.05),细胞的凋亡率显著增加(P<0.05);HHT与IM联合可显著抑制K562/G01细胞内的p-Tyr及p-Crkl的表达水平,并能使p210蛋白及其下游通路蛋白P13K和p-Akt的表达水平明显降低。结论:HHT联合IM可协同抑制K562/G01细胞增殖并诱导其凋亡,其机制可能与抑制p210蛋白表达及其激酶活性有关。

Objective：To explore the effect of homoharringtonine（HHT） combined with imatinib（IM） on proliferation and apoptosis of K562/G01 cells and its potential mechanism.Methods：K562/G01 cells were cultured with HHT and/or IM.CCK-8 assay was used to detect cell proliferation.Cell apoptosis and phosphorylated tyrosine levels were analyzed by flow cytometry.The expression levels of p210,PI3 K,p-Akt and Akt protein were determined by Western blot.Results：Compared with HHT or IM alone,drug combination significantly inhibited cell proliferation and induced apoptosis of K562/G01 cells（both P 〈0.05）.HHT combined with IM could inhibit the levels of phosphorylated tyrosine and phosphorylated Crkl and downregulate the expressions of p210,PI3 K and p-Akt in K562/G01 cells.Conclusion;HHT combined with IM can synergistically inhibit proliferation and induce apoptosis of K562/G01 cells by suppressing the p210 expression and its kinase activity.