转染肿瘤坏死因子-α及MDR1反义RNA逆转乳腺癌多药耐药的研究

目的：转染肿瘤坏死因子-α(TNF-α)cDNA和多药耐药基因(MDR1)的反义RNA到乳腺癌耐药细胞株MCF-7/ADR中进行表达，并观察它们在乳腺癌耐药逆转中的作用。 方法：应用RT-PCR和DNA重组技术构建反义绿色荧光蛋白pEGFP-MDR1融合蛋白表达载体和红色荧光蛋白pDsRed2-TNF-α融合蛋白表达载体，分别和同时导入乳腺癌耐药细胞株MCF-7/ADR中进行表达，检测转染前后细胞的生长曲线、细胞凋亡程度、MDR1-mRNA和P糖蛋白（P-gp）表达情况及对ADR敏感性的变化。 结果：转染后的细胞生长明显减慢，凋亡率显著增加，MDR1-mRNA和P糖蛋白（P-gp）表达明显降低，对ADR的耐药性明显下降，敏感性增加。 结论：联合运用不同的逆转耐药机制，将TNF-α cDNA及MDR1反义RNA分别或同时导入乳腺癌耐药细胞中，能有效达到逆转耐药的目的。

Reversal of multidrug resistance by transfection of tumor necrosis factor α and MDR1 antisense RNA into multidrug resistant breast cancer cell line

AIM: To study the reversal effects of multidrug resistance by transfecting tumor necrosis factor α (TNF-α) cDNA and multidrug resistant 1 (MDR1) gene antisense RNA into multidrug resistant breast cancer cell line MCF-7/ADR. METHODS: The recombinant vector of enhanced green fluorescent protein (EGFP) with MDR1 antisense RNA and recombinant vector of red fluorescent protein (DsRed2) with TNF-α cDNA were constructed by RT-PCR and DNA recombinant techniques. The recombinant vectors were transfected into multidrug resistant breast cancer cell line MCF-7/ADR. The cell growth curves, cell apoptosis rates, MDR1 gene expression at mRNA and P-gp levels, and the sensitivity to ADR were determined before and after the transfection. RESULTS: After the transfection, cells showed lower growth rate, higher apoptosis rate, lower MDR1 expression at mRNA and P-gp levels, and the sensitivity to ADR increased significantly. CONCLUSION: Transfection of TNF-α cDNA and MDR1 antisense RNA into multidrug resistant breast cancer cells may have good effects on reversal of multidrug resistance.