酪氨酸激酶抑制剂STI571对K562细胞周期及相关基因表达的研究  

Effect of protein kinase inhibitor STI571 on the growth and apoptosis of K562 cells and the expression of the ATM/ATR gene

作　　者：李婉红[1] 陈琪[1] 王伶俐[2] 

机构地区：[1]浙江省台州市中心医院检验中心,台州318000 [2]温州医学院第二附属医院检验科,温州325000

出　　处：《现代免疫学》2010年第1期64-67,共4页Current Immunology

摘　　要：为了探讨不同浓度STI571对K562细胞ATM(ataxia telangiectasia mutated)/ATR(ATM-Rad3-Related)基因表达的影响及相应的细胞周期变化和细胞凋亡机制。以不同剂量的STI571作用于K562细胞株,通过联苯胺、吉姆萨2瑞氏染色和流式细胞术证实其分化方向,RT-PCR半定量检测ATM/ATR基因表达,流式细胞术检测BCL-2?Annexin-V和细胞周期。结果随药物浓度升高,K562细胞向红系分化明显,ATM基因表达量增强而ATR基因表达量降低,Bcl-2水平下降,细胞凋亡显著,亚二倍体和G1期细胞数增多,S期和G2/M期细胞减少。不加入药物的K562细胞ATM和ATR几乎不表达。ATM和ATR基因表达水平的变化呈现STI571浓度依赖形式,并与细胞周期改变、细胞凋亡和红系分化相关。To investigate the effects of protein kinase inhibitor STI571 on the ATM/ATR mRNA expression and the corresponding dynamic changes of cell cycle and mechanisms of apoptosis erythyroid-leukemia cell line K562 cells were treated with various concentration of STI571 and the cell differentiation model were evaluated by the staining assay of benzidine and Wright-Giemsa and fluorescence activivated cell analyzer.RT-PCR was introduced to semi-quantify the ATM/ATR mRNA expression and flow cytometry was applied to measure the expression of BCL-2,Annexin V and to analyze the cell cycle.It was found that STI571 could induce erythroid differentiation of K562 cells in a dose dependent manner.Increase in the concentration of STI571 resulted in enhanced expression of the ATM gene,while the those of ATR and BCL-2 were decreased.Furthermore,more apoptosis and G1 phase cells with decreased S and G2/M phase cells could be also observed.Neither ATM nor ATR expression in the untreated K562 cells could be demonstrated.It is concluded that the dynamic change of ATM/ATR gene expression is in a manner of STI571 dose-dependent involving in the changes in cell cycle,erythroid differentiation and cell apoptosis.

关 键 词：酪氨酸激酶抑制剂 STI571 ATM/ATR基因 细胞周期变化 

分 类 号：R733.7[医药卫生—肿瘤] R285.5[医药卫生—临床医学]