Acadesine对K562细胞的增殖抑制作用及其对伊马替尼敏感性增强的影响

Acadesine Inhibits the Proliferation of K562 Cells and Enhances their Sensitivity to Imatinib

目的:探索腺苷酸活化蛋白激酶(AMPK)激动剂Acadesine(AICAR)对K562细胞的增殖抑制作用及对伊马替尼(IM)敏感性的影响。方法:以不同浓度的AICAR单用或联合IM处理K562细胞48 h,应用CCK-8法检测细胞的增殖情况,流式细胞术检测细胞周期分布及凋亡,Western blot检测Cyclin D1、Cyclin E1及Caspase 3蛋白表达水平。结果:AICAR对K562细胞增殖具有抑制作用,且呈浓度依赖性,其48 h的IC_(50)为0.45 mmol/L;AICAR可诱导K562细胞发生G_1期阻滞并可下调Cyclin D1和Cyclin E1蛋白的表达水平,但不能诱导其凋亡发生;AICAR与IM联用与单用相比,K562细胞的增殖活性明显被抑制(P<0.05)。结论:AICAR可通过阻滞细胞周期抑制K562细胞增殖,且与IM具有协同作用。

Objective:To investigate the effects of AMPK agonist Acadesine(AICAR) on growth inhibition of K562 cells and their sensitivity to imatinib(IM).Methods:K562 cells were cultured with different concentrations of AICAR alone or its combination with IM for 48 hours,the CCK-8 assay was used to detect cell proliferation,the cell cycle distribution and apoptosis were analyzed by flow cytometry.The expression levels of Cyclin D1,Cyclin E1 and Caspase 3 protein were determined by Western blot.Results:AICAR inhibited the proliferation of K562 cells in dosedependent manner,and their IC_(50) value was 0.45 mmol/L at 48 hours.AICAR could induce arrest of K562 cells in G_1phase and down-regulated the protein expression levels of Cyclin Dl and Cyclin El;whereas it didn't influence the cell apoptosis.Additionally,the growth inhibition of cells induced by IM was enhanced by AICAR.Conclusion:AICAR can inhibit the proliferation of K562 cells by arresting the cell cycle and enhancing the sensitivity of K562 cells to IM.