外源性TNF-α基因联合异搏定、三苯氧胺逆转多药耐药性  

Reversal of Multidrug Resistance of Exogenous TNF-α Gene Combined with Verapamil or Tamoxifen

作　　者：郭伟剑[1] 李杰[1] 沈兆忠[2] 罗建明[2] 钱关祥[3] 孙欲晓[3] 胡亮[3] 

机构地区：[1]上海第二医科大学新华医院肿瘤科,上海200092 [2]复旦大学附属肿瘤医院,上海200032 [3]上海第二医科大学人类基因治疗研究中心,上海200025

出　　处：《复旦学报（医学版）》2001年第2期141-144,共4页Fudan University Journal of Medical Sciences

摘　　要：目的　观察TNF α基因联合异搏定 (VRP)、三苯氧胺 (TAM)逆转多药耐药性 (MDR)的效果。方法　以重组逆转录病毒为载体将TNF α基因导入具MDR表型的人乳腺癌细胞系MCF7/ADR ,经G418抗性筛选获阳性克隆MCF7/ADR TNF。以PCR与ELISA法检测目的基因的整合与表达。MTT法检测外源性TNF -a基因联合VRP、TAM的逆转MDR作用 ,应用公式I=d/D1+d/D2 分析联合逆转效应。结果　MCF7/ADR -TNF细胞中有TNF α基因的整合和表达 ,TNF α分泌量为 1737pg/ml(10 6cells/ 48h)。与阴性对照细胞相比 ,MCF7/ADR -TNF细胞对ADR的耐药性明显降低 (P <0 .0 5 ) ,耐药逆转倍数为 1.6倍。TNF α基因与VRP联合呈拮抗效应 ,而TNF α基因与TAM (6 μmol/L)联合对MCF7/ADR的耐药性逆转有明显的协同效应 (效应指数I=0 .6 4)。结论　外源性TNFPurpose To study the reversal effect on multidrug resistance (MDR) by TNF?α gene combined with verapamil (VRP) or tamoxifen (TAM). Methods By using recombinant retrovirus vector,TNF?α gene was transfected into multidrug resistant human breast cancer cell line MCF7/ADR.The TNF?α secreting cell clone MCF7/ADR TNF was obtained by G418 screening.The integrating and secreting of TNF?α were analyzed by PCR and ELISA.MTT assay and formula“I=d/D 1+d/D 2'were used to evaluate the reversal effect of multidrug resistance with TNF?α gene combined with verapamil or tamoxifen. Results The level of TNF?α secreted by MCF7/ADR TNF was 1 737 pg/ml (10 6cells/48 h).Compared with control,the resistance to ADR of MCF7/ADR TNF was reversed by 1.6 times.The reversal effect produced by combination of TNF?α gene and VRP was antagonistic.The combination of TNF?α gene and TAM produced synergic effect (interaction index I=0.64). Conclusions TNF?α gene combined with TAM has synergic effect on reversing MDR.

关 键 词：多药耐药性 肿瘤坏死因子-α 异博定 三苯氧胺 肿瘤 药物治疗 

分 类 号：R730.53[医药卫生—肿瘤] R969.4[医药卫生—临床医学]