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目的探讨肿瘤坏死因子α(TNFα)作为多药耐药(MDR)逆转剂,特别是作为多重MDR逆转剂的作用及其机制。方法用本单位建立的肝癌SMMC7721MDR亚系作为MDR模型,用MTT法观察TNFα对MDR的逆转作用,用RT-PCR、流式细胞术观察TNFα对MDR基因表达的影响。结果TNFα对mdr1、LRP、GSTP1和TopoⅡα基因介导的耐药性逆转率为87.52%~100%,对MRP基因介导的耐药性无逆转作用,对多重MDR细胞耐药性的逆转率为76.28%~100%。TNFα对mdr1、LRP、和GSTP1基因的表达有下调作用,对TopoⅡα基因的表达有上调作用,对MRP基因的表达无影响。结论体外细胞实验证实TNFα为多重MDR逆转剂。
Objective To investigate the role of tumor necrosis factor-α (TNFα) as a multidrug resistance (MDR) reversal agent, especially as a multiple MDR reversal agent. Methods The MDR model of SMMC7721MDR subclones established in this unit was used to observe the reversal effect of TNFα on MDR. The effect of TNFα on MDR gene expression was observed by RT-PCR and flow cytometry. Results The reversal rate of TNFα-mediated resistance to mdr1, LRP, GSTP1, and TopoIIα genes was 87.52% to 100%. There was no reversal of MRP gene-mediated drug resistance, and resistance to multiple MDR cells was reversed. The rate is 76.28% to 100%. TNFα down-regulated the expression of mdr1, LRP, and GSTP1 genes, up-regulated TopoIIα gene expression, and had no effect on MRP gene expression. Conclusion In vitro experiments confirmed that TNFα is a multiple MDR reversal agent.