细胞周期蛋白依赖性激酶抑制剂LS-007在急性淋巴细胞白血病中作用及机制

摘要

目的:研究细胞周期蛋白依赖性激酶(CDK)抑制剂LS-007在急性淋巴细胞白血病中的作用及其机制.方法:培养急性淋巴细胞白血病细胞株,以LS-007、夫拉平度、ABT-199等药物处理细胞,然后用mRNA定量和PCR免疫蛋白印迹方法检测白血病细胞内凋亡相关因子mRNA和蛋白含量的变化.用凋亡试剂盒检测细胞凋亡情况.结果:mRNA定量和免疫蛋白印迹检测结果表明,经LS-007处理的急性淋巴细胞白血病细胞中抗凋亡蛋白含量显著下降,LS-007和ABT-199联合使用可促进细胞凋亡,效果更佳.结论:LS-007可以影响RNA聚合酶位点磷酸化,从而改变细胞依赖性周期蛋白激酶,促进细胞凋亡,在急性淋巴细胞白血病的缓解中具有一定的积极意义.%Objective:To study the effect of cyclin dependent kinase(CDK) inhibitor LS-007 on acute lymphoblastic leukemia and its mechanism.Methods:The acute lymphocytic leukemia cell line was cultured and treated by LS-007,flavopiridol and ABT-199,then the changes of apoptosis-related factor mRNA and protein levels were detected by using mRNA quantitative PCR and Werstern blot.Results:quantitative PCR and Western blot detection showed that the levels of antiapoptotic protein decreased significantly in acute lymphoblastic leukemia cells after LS-007 treatment,and the proapoptotic effect of LS-007 combined with ABT-199 was much better.Conclusion:LS-007 can affect the phosphorylation of RNA polymerase sites and promote cell apoptosis through changing the activities of CDK,thus having some positive significance for relieving acute lymphoblastic leukemia.