酪氨酸激酶抑制剂STI571治疗慢性粒细胞白血病的研究  

Research of STI571( a tyrosine- kinase inhibitor) to treat chronic myeloid leukemia

作　　者：王玮[1] 孙秉中[2] 药立波[3] 刘新平[3] 

机构地区：[1]解放军第175医院血液科,福建省漳州市363000 [2]第四军医大学西京医院血液科,西安市710032 [3]第四军医大学生物化学和分子生物学教研室,西安市710032

出　　处：《实用医学杂志》2005年第19期2108-2111,共4页The Journal of Practical Medicine

基　　金：国家自然科学基金资助(编号:39770336)

摘　　要：目的:研究特异性酪氨酸激酶抑制剂STI571对慢性粒细胞白血病(简称慢粒)细胞增殖、凋亡、周期调控及bcr-abl融合基因表达的影响,为慢粒的基因治疗提供理论依据。方法:细胞培养慢粒急变细胞系K562细胞株,通过MTT检测STI571作用下细胞存活率,流式细胞仪检测周期变化,电镜及DNA电泳检测细胞凋亡,半定量RT-PCR检测STI571对bcr-abl融合基因表达的影响。结果:STI571作用后K562细胞中G1期细胞明显增加,S期细胞明显减少。流式细胞图中的二倍体峰前可见一明显亚二倍体峰———凋亡峰(apoptosispeak),提示STI571能明显诱导K562细胞凋亡。电镜发现STI571作用于K562细胞12～72h后,诱导出各期凋亡细胞及凋亡小体。半定量PCR灰度扫描结果显示bcr-abl基因的mRNA表达下降,电泳检测扩增产物,荧光亮度减弱。结论:STI571能明显抑制白血病细胞增殖,细胞阻滞于G0/G1期,且具有明显的诱导凋亡作用,反馈抑制bcr-abl融合基因的表达。Objective To explore the effect of STI571 （a selective tyrosine-kinase inhibitor to abl-protein） on the proliferation, cycle, apoptosis and bcr-abl fusion gene of chronic myelogenous leukemia（CML）, Methods After K562 cells（leukemia cell line）were cultured , the cell survival rate was tested by MTT, cell cycle and apoptosis were tested by flow cytometry, DNA electrophoresis and electron microscope, and bcr-abl fusion gene were tested by RT-PCR. Results When K562 cells were effected by STI571, cell survival rate declined, the cells cycle were arrested in G0/G1 phase and cells in S phase were reduced, apoptosis could be observed by many methods, and reduced expression of bcr-abl fusion gene could tested by RT-PCR. Conclusion STI571 can inhibit the proliferation of K562 cell obviously,regulate cell cycle, induce K562 cell apoptosis, and inhibit expression of bcr-abl fusion gene reactively.

关 键 词：蛋白质酪氨酸激酶 白血病 髓样 慢性 细胞周期 凋亡 STI571 BCR-ABL融合基因 慢性粒细胞白血病 酪氨酸激酶抑制剂 基因治疗 K562细胞凋亡 

分 类 号：R733.72[医药卫生—肿瘤] R733.7[医药卫生—临床医学]