阿糖胞苷及云南霉素的细胞周期阻滞作用研究

Cytosine arabinoside induced different cell cycle arrests from its analog yunnannmycin

目的:阿糖胞苷(cytosinearabi-noside)及其核苷类似物是治疗血液肿瘤的重要药物。研究阿糖胞苷诱导肿瘤细胞的周期阻滞和凋亡,并探讨其相关的机制。方法:本研究使用流式细胞仪检测细胞周期改变及凋亡的诱导;用Westernblot分析肿瘤细胞凋亡和增殖相关蛋白的表达改变。结果:阿糖胞苷诱导KB细胞和HL-60细胞阻滞在G1期,而其胞嘧啶类似物云南霉素将细胞阻滞在G2/M期,但两者最终都诱导细胞凋亡。阿糖胞苷和云南霉素诱导细胞凋亡都伴有c-myc蛋白表达水平下降,阿糖胞苷作用KB细胞后,可观察到p53蛋白和Fas蛋白水平逐渐增高。结论:阿糖胞苷及其胞嘧啶类似物云南霉素诱导不同的细胞周期阻滞。阿糖胞苷诱导细胞凋亡可以通过p53/Fas蛋白依赖和非依赖两条途径来实现。

OBJECTIVE：Cytosine arabinoside and its nucleoside ana logs are important drugs in the treatment of hematologic malignancies. This study is to investigate cell cycle perturbation and apoptosis induced by cytosine arabinoside, and the related mechanisms. METHODS： Flow cytome try was used to investigate the changes of cell cycle and the induction of apoptosis. Western blot analysis was used to observe the aheration of related protein levels. RESULTS： Cytosine arabinoside arrested both HL-60 and KB cells in G1 phase, whereas＇its cytosine analog yunnanmycin arrested the cancer cells in G2/M phase. However, they both ultimately caused cell apoptosis. Either cytosine arahinoside or yunnanmycin induced-apoptosis was accompanied by the depressed expression of e-myc protein. A gradually increased protein levels of both p53 and Fas were observed in KB cells at different time after cytosine arabinoside treatment. CONCLUSION： Cytosine arabinoside blocks both HL-60 and KB cells in G1 phase, while its cytosine analog yunnanmycin arrests the cells in G2/M phase. The apoptosis induced by cytosine arabinoside may go through both p53/Fas-dependent and independent pathway in different cell types.