癌症2001，Vol.20Issue(4)：383-386,4.
外源性TNF-α基因克服多药耐药性的初步研究
Preliminary Study on Conquering Multidrug Resistance with Exogenous TNF-α Gene Therapy
郭伟剑 1钱关祥 2胡亮 2孙欲晓 2沈兆忠 3罗建明 3郑颂国3
作者信息
- 1. 上海第二医科大学附属新华医院肿瘤科,
- 2. 上海第二医科大学人类基因治疗研究中心,
- 3. 复旦大学医学院附属肿瘤医院分子生物学实验室,
- 折叠
摘要
Abstract
Objective： This study was designed to evaluate TNF-α gene therapy for conquering multidrug resistance(MDR). Methods： By using recombinant retrovirus vector, TNF-α gene was transfected into multidrug-resistant human breast cancer cell line MCF-7/Adr. The TNF-α secreting cell clone MCF-7/Adr-TNF1 and MCF-7/Adr-TNF2 were obtained by G418 selection. The integrating and secreting of TNF-α were analyzed by PCR and ELISA method. Cell growth inhibiting and reversal effect of MDR on MCF-7/Adr cells by TNF-α gene were examined by cell account and MTT assay. The changing of intracellular ADR accumulation was analyzed by flow cytometric assay. Results： The level of TNF-α secreted by MCF-7/Adr-TNF1 and MCF-7/Adr-TNF2 were 1737 pg/ml (106 cells/48 h) and 2875 pg/ml respectively. Cancer cells showed lower growth rate after transfection, and the inhibition of growth rate were 32.4％ and 54.8％ in MCF-7/Adr-TNF1 and MCF-7/Adr-TNF2 in comparison with the control, respectively. At the same time, the resistance to ADR were reversed by 5.2 times and 19.3 times, and the intracellular ADR accumulation increased significantly. Conclusion： Drug resistance could be conquered by TNF-α gene therapy. Increasing intracellular drug accumulation may be the mechanism of reversing drug resistance.关键词
乳腺肿瘤/治疗/多药耐药/肿瘤坏死因子-α/基因治疗分类
医药卫生引用本文复制引用
郭伟剑,钱关祥,胡亮,孙欲晓,沈兆忠,罗建明,郑颂国..外源性TNF-α基因克服多药耐药性的初步研究[J].癌症,2001,20(4):383-386,4.
