SODD和Survivin在化疗药物诱导白血病细胞凋亡中的作用  

Effects of SODD and Survivin on Leukemia Cell Apoptosis Induced by Chemotherapeutic Drugs

作　　者：陶红芳[1] 胡群[1] 方建林[2] 刘爱国[1] 刘双又[1] 张柳清[1] 胡迎[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院儿科,武汉430030 [2]华中科技大学同济医学院附属协和医院放射科,武汉430022

出　　处：《中国实验血液学杂志》2007年第3期501-505,共5页Journal of Experimental Hematology

基　　金：国家自然科学基金资助项目;编号39970778

摘　　要：为了研究死亡结构域沉默子(SODD)、survivin、caspase3、caspase8及caspase9在化疗药物诱导白血病细胞凋亡中的变化,以进一步明确凋亡调控基因的调控机制和寻找药物作用新靶点,采用Annexin V/PI双标记流式细胞术检测化疗药物作用后Jurkat细胞凋亡发生率;采用免疫印迹法分析SODD、caspase3、caspase8及caspase9蛋白表达的变化;采用RT-PCR检测survivin mRNA表达的变化;采用免疫组织化学SABC法检测survivin蛋白表达的变化。结果表明:SODD及survivn高表达均抑制肿瘤细胞凋亡,VCR具有时间依赖性特异下调SODD蛋白的功能并能有效诱导Jurkat细胞凋亡,在该凋亡过程中caspase3、caspase8酶原呈时间依赖性逐渐被水解剪切,而caspase9及survivin均无明显变化趋势。结论:SODD参与了VCR诱导白血病细胞凋亡过程,VCR通过下调SODD表达并启动受体配体介导途径诱导Jurkat细胞凋亡,在该过程中线粒体凋亡途径并未被启动。This study was aimed to investigate the changes of silencer of death domains （SODD）, survivin, caspase 3, caspase 8 and caspase 9 in the apoptotic process of human leukemia cells induced by chemotherapeutic drugs in order to explore the molecular mechanism of apoptotic modulatory genes and to search for the new target of chemotherapeutic drugs. After Jurkat cells were induced by chemotherapeutic drugs, the translocated phosphatidylserine was labeled with annexin V/PI, and the apoptosis incidence was measured by FCM; The expression changes of SODD, caspase 3, caspase 8 and caspase 9 were determined by Western blot; the changes of survivin mRNA and protein were determined by RT-PCR and immunohistochemistry SABC method respectively. The results indicated that high expressions of SODD and survivin could inhibit apoptotic signaling pathway ; VCR down-regulated the function of SODD protein and effectively induced the apoptosis of Jurkat ceils in a time-dependent manner and activates caspase 3 through the death receptor-mediated activation of caspase 8, in which caspase 9 and survivin were not degraded. It is concluded that SODD participates in the apoptotic process induced by VCR which induces the Jurkat cell apoptosis by downregulating expression of SODD protein and priming death receptor pathway. In the apoptotic process, the mitochondrion apoptotic pathway is not trigged.

关 键 词：白血病 SODD SURVIVIN 化疗药物 细胞凋亡 

分 类 号：R733.7[医药卫生—肿瘤] R979.1[医药卫生—临床医学]