人肿瘤细胞核苷酸切除修复蛋白表达与抗癌药耐药的相关性(英文)  

Nucleotide Excision Repair Protein Levels vis-à-vis Anticancer Drug Resistance in 60 Human Tumor Cell Lines

作　　者：陈忠平[1] Areti MALAPETSA Anne MONKS Timothy G. MYERS Gérard MOHR Eaward A. SAUSVILLE Dominic A. SCUDIERO Lawrence C. PANASCI 

机构地区：[1]中山大学肿瘤防治中心,广东广州510060 [2]Lady Davis Institute for Medical Research,Sir Mortimer B. Davis-Jewish General Hospital [3]Frederick Cancer Research and Development Center,frederickmd21702 [4]Information Technology Branch,National Cancer Institute,rockvillemd20852 [5]Developmental Therapeutics Program,National Cancer Institute

出　　处：《癌症》2002年第3期233-239,共7页Chinese Journal of Cancer

基　　金：(美国)NationalCancerInstituteContract;(加拿大)AprivatedonationfromHelenandNickiLang;CMB-SUMSScholarshipProgram(98-677);中山大学肿瘤防治中心启动基金项目(433);教育部留学回国人员基金项目(2000)

摘　　要：背景与目的:核苷酸切除修复(Nucleotideexcisionrepair,NER)是真核细胞中的DNA修复多酶系统,它可能与人肿瘤细胞对抗癌药的耐药有关。本实验将探讨NER蛋白(XPA,XPB,XPD和ERCC1)的表达与人肿瘤细胞耐药的关系。方法:采用westernblot检测美国国家癌症研究所(NationalCancerInstitute,NCI)用于抗癌药筛选的60株人肿瘤细胞的ERCC1,XPA,XPBXPD表达,并与170种抗癌药物的细胞毒试验结果进行相关性分析。结果:ERCC1,XPB和XPD的蛋白表达与抗癌药物敏感性呈负相关,在170种抗癌药物中分别有13,17和32种的耐药性与上述蛋白水平相关性显著或非常显著(P<0.05)。而XPA的表达与药物敏感性无明显正/负相关。根据已确定的6种药物作用机理分析,肿瘤细胞XPD表达与其对烷化剂类抗癌药耐药相关性显著。结论:本实验结果肿瘤细胞的XPD蛋白表达与烷化剂类抗癌药的耐药相关,提示XPD在肿瘤细胞耐药过程中起重要作用。Background &Objective:Nucleotide excision repair(NER)is a multi-enzyme DNA repair system i n eukaryotes.Several NER genes in thi s system including XPA,XPB,ERCC1,and ERCC2(XPD)have been implicated in anticancer drug resistance in human tumor cells.This study was designed to investigate the relatio nship between the expression of NER protein and the drug-resistance of human tumor cell lines.Methods:In this study,The authors assessed t he levels of the above mentioned proteins,by utiliz ing Western blot analysis,in the USA National Cancer Institute(NCI )panel of 60humantumor cell lines and correlated to th e cytotoxicity patterns of 170compounds that constitute the standard agent (SA)database.Results:The ERCC1,XPB,and XPD protein expre ssion patterns yielded significant negative Pearson correlations with 13,17,and 32out of the 170compounds,respectively(P<0.05).XPA produced a random assortment of negative and positive correlations and did not appear to confer an overall resista nce or sensitivity to these drugs.Pr otein expression was also compared with a pre-defined categorisation of the standard agen ts into six mechanism-of-action(MOA)groups resulting in an inverse association between XPD and alkylating agent sen sitivity.Conclusion:Our present data demonstrate that XPD protein levels correlate wi th resistance to alkylating agents i n human tumor cell lines,suggesting that XPD plays an important role in the development of this resistance.

关 键 词：核苷酸切除修复 肿瘤耐药性 烷化剂 NER 真核细胞 

分 类 号：R73-36[医药卫生—肿瘤]