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人肺腺癌亲代与耐顺铂细胞系耐药与凋亡相关基因表达差异及其相关性
引用本文:李西平,刘叙仪,王洁,王曾礼,蒋薇,张毅,刘元林.人肺腺癌亲代与耐顺铂细胞系耐药与凋亡相关基因表达差异及其相关性[J].中国呼吸与危重监护杂志,2003,2(2):79-82.
作者姓名:李西平  刘叙仪  王洁  王曾礼  蒋薇  张毅  刘元林
作者单位:1. 四川大学华西医院呼吸内科,四川成都,610041
2. 北京大学临床肿瘤学院内二科
3. 军事医学科学院基础医学研究所
基金项目:国家“九五”课题攻关资助项目 ( 96 90 6 0 1 2 3),北京市自然科学基金资助项目( 7992 0 0 5),北京科技新星计划资助项目 ( 14 8)
摘    要:目的 探讨人肺腺癌亲代与耐顺铂细胞系A549和A549^DDP耐药及凋亡相关基因表达的差异,以及多药耐药的发病机制。方法 采用逆转录-PCR及免疫细胞化学方法检测A549和A549^DDP细胞多药耐药相关蛋白(MRP)、肺耐药蛋白(LRP)、bcl-2及C-erbB-2的表达水平。结果 逆转录-PCR结果显示:A549细胞表达MRP、bcl-2及C-erbB-2mRNA,无LRP mRNA表达,A549^DDP细胞亦表达MRP、bcl-2及C-erbB-2mRNA,且表达LRP mRNA,耐药细胞MRP及C-erbB-2mRNA表达水平较亲代显增高,bcl-2mRNA表达水平与亲代无显性差异(P=0.731);A549^DDP细胞血管生成因子及耐药相关基因mRNA表达水平较A549细胞显增高,差异有显性(P=0.007)。免疫细胞化学结果显示:亲代和耐药细胞bcl-2蛋白表达呈强阳性,亲代C-erbB-2及LRP呈阴性,MRP轻度阳性,耐药细胞MRP蛋白呈中度阳性,C-erbB-2及LRP轻度阳性。结论 A549细胞的原发耐药与耐药及凋亡相关基因MRP、C-erbB-2和Bcl-2的异常表达和协同作用有关。A549^DDP细胞MRP和C-erbB-2的表达增强,且表达LRP,可能是继发耐药的产生机制。

关 键 词:人肺腺癌亲代  耐顺铂细胞系  细胞凋亡  基因表达  肺癌  免疫细胞化学  细胞培养  分子生物学
修稿时间:2002年12月1日

Ddifferent expression of multidrug-resistance and apoptosis related genes in human lung adenocarcinoma parental cell line A549 and cisplatin-resistant cell line A549DDP
LI Xiping ,LIU Xuyi,WANG Jie,et al.Ddifferent expression of multidrug-resistance and apoptosis related genes in human lung adenocarcinoma parental cell line A549 and cisplatin-resistant cell line A549DDP[J].Chinese Journal of Respiratory and Critical Care Medicine,2003,2(2):79-82.
Authors:LI Xiping  LIU Xuyi  WANG Jie  
Institution:LI Xiping *,LIU Xuyi,WANG Jie,et al *Department of Respiratory Medicine,West China Hospital,Sichuan University Chengdu,Sichuan 610041,China
Abstract:Objective To investigate the expression difference of multidrug resistance and apoptosis related genes and its contribution to mechanisms of multidrug resistance in human lung adenocarcinoma parental cell line A 549 and cisplatin resistant cell line A 549 DDP Methods RT PCR and Immunohistochemical staining were performed to detect the mRNA expressions and protein production of multidrug resistance related protein (MRP),lung resistance protein (LRP),bcl 2,and C erbB 2 in A 549 and A 549 DDP .Results MRP,bcl 2,and C erbB 2 mRNA were expressed in A 549 ,but no LRP mRNA was detected in A 549 MRP,C erbB 2,and LRP mRNA expression levels in A 549 DDP were significant higher than those in A 549 ,otherwise,LRP mRNA was detected in A 549 DDP There was no difference of bcl 2 mRNA expressions between A 549 and A 549 DDP ( P =0 731) Bcl 2 protein expressions were strongly positive both in A 549 and in A 549 DDP MRP protein expressions in A 549 were faint positive,while C erbB 2 and LRP were negative MRP protein expressions in A 549 DDP was median positive C erbB 2 and LRP protein expressions in A 549 DDP were strongly positive Conclusions The heterogenous expression of MRP,C erbB 2,and LRP in A 549 and A 549 DDP may be associated with primary and secondary drug resistance in lung cancer
Keywords:Lung cancer  Multidrug  resistance  Apoptosis
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