新的肿瘤耐药相关基因ERGIC-53的研究  

Study on A Novel Tumor-Related Drug Resistant Gene ERGIC-53

作　　者：肖瑛[1] 许元富[2] 周圆[2] 邵晓枫[2] 谢印良[2] 谷岳[2] 熊冬生[2] 杨纯正[2] 

机构地区：[1]暨南大学药学院 [2]中国医学科学院血液学研究所实验血液学国家重点实验室

出　　处：《天津医药》2008年第11期836-839,共4页Tianjin Medical Journal

基　　金：国家自然科学基金资助项目(项目编号:30400405;30570772);天津市自然科学基金重点资助项目(项目编号:05YFJZJC01200)

摘　　要：目的:研究ERGIC-53基因表达与肿瘤细胞耐药的关系,寻找肿瘤耐药逆转可能的新靶点。方法:采用Northern Blot检测ERGIC-53基因在K562和K562/A02中的表达差异;应用逆转录聚合酶链反应(RT-PCR)检测11种肿瘤敏感及耐药细胞系中ERGIC-53基因的表达;设计合成针对ERGIC-53基因的siRNAs,用脂质体法转染K562和K562/A02细胞,用MTT比色法和流式细胞仪检测其干扰耐药细胞中ERGIC-53基因表达后的细胞对阿霉素的敏感性。结果:ERGIC-53在K562/A02细胞中的表达明显高于亲代K562细胞(P<0.05);6种耐药细胞株中ERGIC-53基因表达的平均值约为亲代敏感细胞的2倍。siRNA转染组与对照组相比,K562/A02细胞对阿霉素的敏感性均有不同程度的提高,且在转染后72h时细胞内阿霉素积累接近其亲代敏感细胞水平。结论:ERGIC-53基因与肿瘤细胞耐药相关,明确该基因参与耐药肿瘤细胞表型的形成。Objective：To investigate the role of ERGIC-53 gene in tumor drug resistance,and provide a new target for circumventing tumor drug resistance in the future.Methods：The different expression levels of ERGIC-53 between K562/A02 and its parental K562 cell line were determined by Northern blot.The method of RT-PCR was used to detect the expression level of ERGIC-53 in 11 kinds of tumor cell lines,including sensitive and drug resistant cell lines.The siRNA targeted to ERGIC-53 were transfected into K562/A02 by Lipofectamine 2000.The expressions of ERGIC-53 in those transfected cells were analyzed by RT-PCR,and the sensitivity to doxocubicin of K562/A02 was investigated by MTT assay and FACS.Re-sults：The expression level ERGIC -53 was significantly increased,about two -fold higher,in K562/A02 than that in its parental K562 cell line.The siRNA targeted to ERGIC-53 decreased the ERGIC-53 expression level,and significantly in-creased doxocubicin accumulation in K562/A02,and sensitize ERGIC-53-expressing K562/A02 resistance to doxocubicin.Conclusion：ERGIC-53 may play an important role in tumor drug resistance,and further studies are needed for a clear un-derstanding of the molecular mechanism of this novel drug resistant-related gene.

关 键 词：抗药性 多药 抗药性肿瘤 RNA干扰 抗肿瘤药 基因 

分 类 号：R730.5[医药卫生—肿瘤] R733.7[医药卫生—临床医学]