乳腺癌耐药蛋白在肝癌多药耐药中的作用及其机制探讨  

The role of BCRP in hepatocellular carcinoma multidrug resistance and mechanism

作　　者：李高鹏[1] 陈孝平[1] 叶露[1] 王其[1] 徐宗全[1] 张万广[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院肝脏外科中心,武汉430030

出　　处：《腹部外科》2006年第5期301-303,共3页Journal of Abdominal Surgery

基　　金：卫生部临床学科重点项目(卫规财发[2001]321号)

摘　　要：目的研究乳腺癌耐药蛋白(breastcancer resistance protein,BCRP)在肝癌中的表达及其意义。方法通过培养液中ADM浓度递增诱导法筛选培养,建立HepG2/ADM肝癌多药耐药细胞株;采用荧光定量PCR及免疫组织化学技术,分别在mRNA和蛋白质水平检测BCRP在正常肝细胞系L02、肝癌细胞系HepG2及HepG2/ADM与未经化疗的癌组织、多次化疗后的癌组织、癌旁组织的表达差异。结果HepG2/ADM的BCRPmRNA表达是HepG2的9倍(P<0.01);L02和HepG2中BCRPmRNA的表达无差异(P>0.05);化疗后病人癌组织BCRPmRNA平均表达是未化疗病人癌组织的4.2倍(P<0.01);化疗病人癌组织BCRPmRNA平均表达是癌旁组织的3.4倍(P<0.01);未化疗病人癌和癌旁组织间的表达无差异(P>0.05);免疫组织化学显示BCRP在胞膜表达;BCRPmRNA和蛋白表达具有一致性。结论HepG2/ADM多药耐药细胞株是一个较好的研究肝癌多药耐药的模型。BCRP基因在正常肝细胞中表达,而在多次化疗后的病人和HepG2/ADM中表达上调,提示化疗药物诱导BCRP的表达,BCRP的高表达与肝癌多药耐药有关。Objective To study the expression of breast cancer resistance protein（ BCRP） in hepatocellular carcinoma（HCC） and its significance. Methods HepG2 cell line resistant to adriamycin （HepG2/ADM）was induced by increasing concentration of ADM step by step. The expression of BCRP protein and mRNA was detected by real-time RT-PCR and immunohistochemistry respectively in normal hepatocellular line L02, HCC lines HepG2 and HepG2/ADM, HCC tissues without chemotherapy, HCC tissues after therapies and para-tumor tissues. Results The expression of BCRP mRNA in HepG2/ADM cells was 9 times of HepG2 cells（P〉0. 01） ;there was no difference in the BCRP mRNA expression between HepG2 cells and L02 cells（P〉0. 05） ;the expression of BCRP in HCC tissues after chemotherapy was 4. 2 times of that in HCC tissues without chemotherapy（P〈0. 01） ;in the patients subject to chemotherapy, the expression of BCRP mRNA in tumor tissues was 3. 4 times of para-tumor tissues;in patients without subject to chemotherapy, there was no difference in the BCRP mRNA expression between tumor and para-tumor tissues; immunohistochemistry revealed that BCRP was mainly expressed in the cell membrane; the expression of BCRP protein was in coincidence with the expression of MRNA. Conclusion HepG2/ADM is a good model for the study of MDR. BCRP gene was expressed in normal liver cells. The expression of BCRP was up-regulated in the patients subject to chemotherapies and HepG2/ADM cell line, suggesting anticancer agents could induce the expression of BCRP and the high expression of BCRP was related with the MDR of HCC.

关 键 词：肝肿瘤 抗药性 多药 免疫组织化学 

分 类 号：R735.7[医药卫生—肿瘤]