多药耐药细胞MCF-7/ADR及其亲本细胞MCF-7人类白细胞抗原和B7表达的对比研究  

Expression of HLA and B7in multidrug-resistant breast cancer cell line MCF-7/ADR and its parent cell line MCF-7

作　　者：但汉雷[1] 赵燕[1] 张健[1] 张积仁[1] 

机构地区：[1]第一军医大学珠江医院全军肿瘤医学中心,广东广州510282

出　　处：《第一军医大学学报》2001年第10期731-734,共4页Journal of First Military Medical University

基　　金：国家自然科学基金(39870813);广东省自然科学基金(001041)

摘　　要：摘要:目的研究乳腺癌多药耐药细胞人类白细胞抗原(HLA)和免疫共刺激分子B7的表达,探讨乳腺癌多药耐药与免疫逃避的关系。方法应用免疫荧光-单克隆抗体直接标记的流式细胞技术,检测并分析比较阿霉素和长春新碱耐药的乳腺癌细胞(MCF-7/ADR)及其化疗敏感的亲本细胞(MCF-7)HLA和B7分子(B7-1/CD80、B7-2/CD86)的表达。结果MCF-7/ADR细胞多药耐药糖蛋白P-170表达的阳性细胞百分率(PECR)和平均相对荧光强度(RLFI)分别为85.3%和40.65±5.54,明显高于MCF-7细胞(分别为3.38%、5.13±3.27,P<0.001、P=0.0030)。MCF-7/ADR细胞HLA-Ⅰ表达的PECR和平均RLFI分别为76.26%和51.77±7.55,明显低于敏感细胞MCF-7(分别为98.22%和129.08±9.97,P<0.001);MCF-7/ADR细胞HLA-DR的PECR和平均RLFI分别为13.92%、19.20±5.23,MCF-7细胞分别为10.06%、19.20±5.23;两种细胞B7-1表达的PECR和平均RLFI没有显著差异(P=0.348,P=0.105)。敏感细胞B7-2表达的PECR为14.4%,平均RLFI为11.72±4.15,MCF-7/ADR细胞分别为1.28%(P=0.011)、30.06±3.20(P=0.026)。结论乳腺癌多药耐药细胞HLA和B7分子表达与敏感细胞有显著区别,主要表现为HLA-Ⅰ类分子表达下调,表明乳腺癌多药耐药细胞存在HLA-I相关的免疫逃避机制。Objective To studytheexpressionof HLA andco-stimulatorymoleculesB7in humanbreastcancercellswith multidrugresistance(MDR)phenotypeandexplorethe correlationbetweenMDRmechanismsandimmuneevasionof the cancercells.Methods The expressionsof HLA-I,HLA-DR,B7(CD80,CD86)andP-170(a170000membraneprotein encodedby MDRgene)in humanbreastcancercelllineMCF-7and itsadriamycin-resistantsublineMCF-7/ADRwere analyzedcomparativelyusingflowcytometer(FCM).Results MTT assayandFCManalysisindicatedthattheMCF-7/ADR cellswithhigherpositivityratefor P-170expression(85.3%)weremoreresistantto adriamycinandvincristinethanthe MCF-7cells.Thepositivecellpercentageandmeanrelativelinearfluorescenceintensity(RLFI)forHLAclassⅠinMCF-7/ADRcellswere76.26%and51.77±7.55respectively,significantlylowerthanthosein MCF-7cells(98.22% and129.08±9.97,P<0.001).The2indicesforHLAclassⅡinMCF-7/ADRcellswere13.92%and19.20±5.23,alsolowerthanthose measuredinMCF-7cells(10.06%,P<0.001and16.70±2.37,P=0.173).CD80expressioninthe2celllineswassimilarin termsof thepositivecellpercentage(2.08%to1.84%,P=0.348)andthemeanfluorescenceintensity(12.76±2.03to21.13±3.77,P=0.105).CD86-positivecellpercentagein MCF-7/ADRcells(14.4%)washigherthanthatinMCF-7cells(1.28%,P=0.001),buttheRLFIof CD86inMCF-7/ADRcells(11.72±4.15)was lowerthanthatin MCF-7cells(30.06±3.20,P=0.026).Conclusions Significantlydown-regulatedHLA classⅠexpressionand enhancedHLA classⅡexpressionalongwith alteredexpressionof B7moleculesarepresentinMCF-7/ADRcells,indicatingthatthedown-regulationof HLA-Ⅰmolecule expressionmaybe oneof theimportantmechanismsof immuneevasioninMDRbreastcancercells,whichmaybe reversed by up-regulationof HLA-Ⅰexpression.

关 键 词：乳腺肿瘤 药物耐受性 HLA抗原 免疫共刺激分子 多药抗药性 

分 类 号：R730.3[医药卫生—肿瘤]