表阿霉素对肝癌亚细胞蛋白质组影响的研究  

PROTEOMIC APPROACH TO THE EFFECT OF EPIRUBICIN ON HEPATOMA CELLS AT SUBCELLULAR LEVEL

作　　者：李兴[1] 潘卫[2] 邱峰[3] 邱宗荫[1] 

机构地区：[1]重庆医科大学医学检验系,重庆400016 [2]贵阳医学院医学检验系,贵阳550004 [3]重庆医科大学药学系,重庆400016

出　　处：《分子细胞生物学报》2006年第5期407-413,共7页Journal of Molecular Cell Biology

基　　金：国家自然科学基金(30476021);教育部博士点基金(教特发中心函[2004]166号)资助项目

摘　　要：表阿霉素是临床应用的抗癌药物之一,它干扰DNA的复制和转录,并能诱导癌细胞凋亡。表阿霉素对癌细胞蛋白质表达谱的影响,涉及到表阿霉素药理作用的机制,对此进行研究,有助于抗癌药物作用机制的理解。运用亚细胞蛋白质组学的研究策略,对比分析表阿霉素干预前后,肝癌细胞线粒体、细胞核蛋白质组的表达差异。通过超离心分离纯化细胞器,双向电泳分离蛋白质,图像分析筛选差异表达蛋白,MALDI-TOF-MS分析鉴定蛋白质。从线粒体、细胞核两个亚细胞组分中一个鉴定了15种差异表达蛋白,其中5种在表阿霉素干预后的肝癌细胞中表达上调,10种干预后表达下调。这些差异表达蛋白质涉及到细胞的能量代谢、蛋白质合成、细胞骨架的改变、mRNA的加工成熟、细胞应急状态的形成及凋亡调控等许多方面。Epirubicin is an antineoplastic agent known as an anthracycline. It acts directly on DNA by blocking its replication and transcription,so apoptosis can be induced for cancer cells. The protein expression of cancer cells will be altered due to the induction of pharmacological action of epirubicin, so it is important to pay attention to the altered profiling of proteins. Here proteomic strategy was applied to the hepatoma cells at subcellular level,comparative proteome analysis of mitochondria and nucleus were conducted between the hepatoma cells administered with epirubicin and the not-administered. Centrifugation was used for the subcellular fractionation,then 2-DE for the separation of proteins,imaging analysis for the diction of expression-altered spots, and MALDI-TOF-MS for the identification of proteins. In total,15 proteins were found to have altered their expression after the induction of epirubicin,among them, 5 proteins showed up-regulated expression and 10 showed down-regulated expression. These altered proteins are involved in life processes of cells such as energy metabolism,protein biosynthesis,structure of cell skeleton, processing and maturation of mRNA, heat shock of cells and apoptosis.

关 键 词：肝癌细胞 蛋白质组学 亚细胞水平 表阿霉素 

分 类 号：R735.7[医药卫生—肿瘤]