Preliminary Study on Conquering Multidrug Resistance with Exogenous TNF-α Gene Therapy
10.3321/j.issn:1000-467X.2001.04.009
- VernacularTitle:外源性TNF-α基因克服多药耐药性的初步研究
- Author:
Wei-Jian GUO
1
;
Guan-Xiang QIAN
;
Liang HU
;
Yu-Xiao SUN
;
Zhao-Zhong SHEN
;
Jian-Ming LUO
;
Song-Guo ZHENG
Author Information
1. Xinhua Hospital of Shanghai Second Medical University
- From:Chinese Journal of Cancer
2001;20(4):383-386
- CountryChina
- Language:Chinese
-
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.
