胶质瘤耐药细胞系中11种ABC转运子的表达  

Expression of Eleven ABC Transporters in BCNU-resistant Glioma Cell Lines

作　　者：谢思明[1,2] 方茅[2] 钟雪云[2] 

机构地区：[1]暨南大学临床医学博士后流动站,广州市510632 [2]暨南大学医学院

出　　处：《中国肿瘤临床》2011年第17期995-998,共4页Chinese Journal of Clinical Oncology

基　　金：中国博士后科学基金(编号:20090450884)资助~~

摘　　要：目的:在胶质瘤的治疗中,亚硝基脲类药物如卡氮芥是常用的化疗药物。但由于耐药性的产生,患者预后通常不良。在耐药机制的研究中,ABC转运子家族因其具有将药物泵出细胞外的特性而备受关注。本研究旨在探讨胶质瘤细胞中卡氮芥耐药与11种ABC转运子的关系。方法:以SWOZ2细胞作为卡氮芥敏感的细胞系,以卡氮芥耐药的SWOZ1细胞作为原发性耐药细胞系,同时诱导出卡氮芥耐药的SWOZ2细胞系作为获得性耐药细胞系,通过CCK-8法测定细胞的生长曲线及卡氮芥对各细胞系的IC50和耐药指数,同时通过荧光定量PCR法检测耐药细胞与敏感细胞中11种ABC转运子mRNA表达的差异。结果:CCK-8法结果表明,与SWOZ2细胞相比,SWOZ1对卡氮芥的耐药性是SWOZ2的4.7倍,SWOZ2的卡氮芥耐药细胞系(命名为SWOZ2/B)对卡氯芥的耐药性是SWOZ2的6.5倍。采用相对定量的荧光定量PCR法检测1 1种ABC转运子在各细胞系中的表达,结果表明只有ABCG1在2株耐药细胞系中均表达上调,分别在SWOZ1中上调了4.1倍、在SWOZ2/B中上调了4.4倍。结论:ABCG1在脑胶质瘤细胞卡氯芥耐药中可能发挥重要作用。Objective： Glioma is one of the most frequently seen malignant tumors in the central nervous system. Alkylating agents such as 1,3-bis（ 2-chloroethyl ）- 1-nitrosourea （ BCNU ） are among the most effective cytotoxic agents for these patients, but the responses remain very poor. The adenosine triphosphate binding cassette （ ABC ） transporter family, whose products represent membrane proteins, have the capability to use energy to drive the transporters of various molecules across the cellular membrane, and are confirmed to be associated with anticancer drug transporters. At present, 11 ABC transporters have been found to be involved in drug resistance. In the present study, the glioma cell lines SWOZ1 and SWOZ2, which were isolated and cloned from the same parental cell line SWO38, were used to investigate the relationship between the expression of 11 ABC transporters and BCNU resistance in gliomas. Methods： The glioma cell line SWOZ2, which is sensitive to BCNU treatment, was taken as the control, and glioma cell line SWOZ1, which is resistant to BCNU, was taken as the intrinsic resistant cell line. BCNU-resistant cells SWOZ2/B, derived from SWOZ2, were taken as the acquired resistant cell line. A CCK-8 assay was used to determine the growth curve of the cells, and also the IC50 values and resistance indices （ RI ） to BCNU of each cell line. Quantitative RT-PCR was used to evaluate the modulation of the expression of the eleven ABC transporters related to drug resistance in these cell lines. Results： No significance was found between the growth curves of the cell lines. Based on the results of the CCK-8 assay, the IC50 value of the cell lines SWOZ1 and SWOZ2/B against BCNU was （ 16.17 ± 1.62 ） and （ 22.38 ± 1.08 ） μg/mL, respectively. The resistance of SWOZ1 and SWOZ2/B were 4.7-fold and 6.5-fold more than that of the cell line SWOZ2 [（ 3.47 ± 0.86 ） gg/mL], respectively. The results of quantitative RT-PCR revealed that only ABCG 1 was overexpressed both in the intrinsic and ac

关 键 词：脑胶质瘤 卡氮芥 ABC转运子 

分 类 号：R739.4[医药卫生—肿瘤]