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)

被引：7

作者：

陈忠平

Areti MALAPETSA

Anne MONKS

Timothy G. MYERS

Gérard MOHR

Eaward A. SAUSVILLE

Dominic A. SCUDIERO

Lawrence C. PANASCI

机构：

[1] 中山大学肿瘤防治中心,LadyDavisInstituteforMedicalResearch,SirMortimerBDavis-JewishGeneralHospital,FrederickCancerResearchandDevelopmentCenter,InformationTechnologyBranch,NationalCancerInstitute,InformationTechnologyBranch,NationalCa

来源：

癌症 | 2002年 / 03期

关键词：

核苷酸切除修复; 肿瘤耐药; 烷化剂;

D O I：

暂无

中图分类号：

R73-36 [治疗实验];

学科分类号：

100214 ;

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。

引用

页码：233 / 239

页数：7

共 27 条

[1]

Displayandanalysisofpatternsofdifferentialactivityofdrugsagainsthumantumorcelllines:developmentofmeangraphandCOMPAREalgorithm犤J犦. PaullKD,ShoemakerRH,HodesL,etal. JNatlCancerInst . 1989

[2]

WorkshoponeukaryoticDNArepairgenesandgeneproducts犤J犦. LehmannAR. Cancer Research . 1995

[3]

XPDmightplayanimportantroleinDNArepair犤J犦. PanasciLC,XuZ. ProcAmAssocCancerRes . 2001

[4]

DNArepaircapacity:inconsistencybetweeneffectofover-expressionoffiveNERgenesandthecorrelationofmRNAlevelsinprimarylymphocytes犤J犦. VogelU,DybdahlM,FrentzG,etal. Mutation Research . 2000

[5]

ThetwomajorsporeDNArepairpathways,nucleotideexcisionrepairandsporephotoproductlyase,aresufficientfortheresistanceofBacillussubtilissporestoartificialUV-CandUV-Bbutnottosolarradiation犤J犦. XueYandNicholsonWL. ApplEnvironMicrobiol . 1996

[6]

SensitivityofCHOmutantcelllineswithspecificdefectsinnucleotideexcisionrepairtodifferentanti-canceragents犤J犦. DamiaG,ImperatoriL,StefaniniM,etal. International Journal of Cancer . 1996

[7]

DNArepairhelicase:acomponentofBTF2(TFIIH)basictranscriptionfactor犤J犦. SchaefferL,RoyR,HumbertS,etal. Science . 1993

[8]

Xerodermapigmentosum,Cockaynessyndrome,helicases,andDNArepair:Whatstherelationship犤J犦. FriedbergEC. Cell . 1992

[9]

Feasibilityofahigh-fluxanticancerdrugscreenusingadiversepanelofculturedhumantumorcelllines犤J犦. MonksA,ScudieroD,SkehanP,etal. JNatlCancerInst . 1991

[10]

CorrelationofchloroethylnitrosourearesistancewithERCC-2expressioninhumantumorcelllinesasdeterminedbyquantitativecompetitivepolymerasechainreaction犤J犦. ChenZP,MalapetsaA,MarcantonioD,etal. Cancer Research . 1996

← 1 2 3 →