磷脂酰肌醇3-激酶/蛋白激酶B信号通路与白血病阿霉素耐药的相关性

Study on the relationship between PI3K/Akt signal transduction pathway and leukemia adriamycin resistant strains K562/ADM cells

目的:探讨白血病阿霉素耐药与磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号转导通路的相关性。方法:选择磷脂酰肌醇3-激酶特异性抑制剂LY294002,将白血病敏感株K562/S和白血病阿霉素耐药株K562/ADM细胞分别给予LY294002和ADM干预,评价LY294002作用前后阿霉素对白血病细胞的抑制作用,检测K562/S和K562/ADM各组细胞PI3K和Akt表达水平。结果:LY294002干预前后不同浓度阿霉素对白血病K562/S和K562/ADM细胞抑制作用具有非常显著性差异(P<0.05);不同浓度LY294002可降低K562/S和K562/ADM细胞中PI3K和Akt表达,LY294002各浓度组与ADM组及对照组组间比较具有非常显著性差异(P<0.05)。结论:磷脂酰肌醇3-激酶/蛋白激酶B信号通路异常与白血病阿霉素耐药有关,抑制磷脂酰肌醇3-激酶/蛋白激酶B信号通路能增强白血病阿霉素敏感性。

OBJECTIVE To investigate the relationship between adriamycin resistance of leukemia and PDK/Akt signal transduction pathway. METttODIS Selecting phosphatidylinositol 3-kinase inhibitor LY294002, leukemia sensitive strains K562 / S and leukemia adriamycin resistant strains K562/ADM cells were treated respectively with LY2941102 and adriamycin inter- vention. MTT assay was used to evaluate the adriamycin inhibition of leukemia cells before and after giving LY294002, and Western blot was used to detect the expression of PI3K and Akt in K562/S and K562/ADM cells. RESULTS Before and after the intervention of LY294002, the inhibitions of leukemia K562/S and K562/ADM ceils caused by different concentrations of adriamycin had a significant difference（P〈0. 01）, and different concentrations of LY294002 could reduce the expression of PDK and Akt in K562/S and K562/ADM cells. There was a very significant difference between different concentrations of LY294002 group and control group （P〈0.01）. CONCLUSION Abnormal PI3K/Akt signal transduction pathway is associated with leukemia adriamycin resistance, and inhibition of PBK/Akt signaling pathway can enhance leukemia adriamycin sensitivity.