Reversal of Adriamycin Resistance in Human Mammary Cancer Cells by Small Interfering RNA of MDR1 and MDR3 Genes / 华中科技大学学报（医学）（英德文版）

ABSTRACT

The purpose of this paper is to investigate the reversal effect of small interfering RNA (siRNA) targeting MDR1 and MDR3 genes on the resistance of MCF-7/ADR cells to adriamycin.siRNA plasmid vector targeting MDR1 and MDR3 genes was transfected into MCF-7/ADR cells, and then was stained with Annexin-V FITC (fluorescein isothiocyanate conjugated) to detect the early stage cell apoptosis by flow cytometry (FCM). 50 ％ inhibition concentration (IC50) of adriamycin for MCF-7/ADR cells was determined by MTT method. MDR1 and MDR3 mRNA was assessed by RT-PCR. Treatment of MCF-7/ADR cells with the two kinds of siRNAs resulted in a reversal of adriamycin resistance of MDR to different extents. 1) The apoptosis efficiency of MDR1 and MDR3siRNA vector after transfection was (18.21±1.65) ％ and (9.07±2.16) ％ respectively (P＜0.05), and there was significant differences in the apoptosis efficiency between pSuppressor Neo vector and the MDR 1 siRNA or MDR3 siRNA vector (P＜0.01); 2 ) The reversal effect of MDR 1 siRNA is higher than that of MDR3 siRNA (P＜0.05); 3 ) The expression of MDR1 and MDR3 mRNA can be restrained by pSuppressor Neo MDR1 and MDR3 siRNA respectively, and the reduction in the mRNA level was in a time-dependent manner (P＜0.01). MDR1 and MDR3 gene silencing can enhance intracellular adriamycin accumulation in MCF-7/ADR cells, improve sensitivity of MCF-7/ADR cells to adriamycin, and induce cell apoptosis. The reversal effect of adriamycin resistance by siRNA of MDRlwas more effective than that of MDR3.