Study on the reversal effect of MDR1 and MRP ASODN on drug-resistance gastric carcinoma cells / 重庆医科大学学报

ABSTRACT

Objective:To investigate the reversal effect of MDR1 and MRP antisense oligodooxynucleotide (ASODN) on adriamycin-resistant SGC7901/ADM cells. Methods:SGC7901/ADM cells were transfected by MDR1 or MRP ASODNs or the combination of two. Then the mRNA expressions of proteins MDR1 and MRP were checked by RT-PCR,and the expressions of P-gp and MRP by immunocytochemistry;the intracellular fluorescence intensity of Rhodamine 123 in these cells were determined by flow cytometry;and the sensitivity of these cells to adriamycin,carboplatin and other anticancer drugs were determined by MTT assay. Results:The expression of MDR1mRNA and MRP mRNA in SGC7901/ADM cells decreased at 12h after transfection of ASODNs,decreased to the lowest level at 24h and returned to the level before transfection after 48h. The expression of P-gp and MRP decreased significantly at 48h after transfection with ASODNs compared with the control cells. The retention of Rhodamine 123 in SGC7901/ADM cells was significantly higher than that before transfection, and the intracellular fluorescence intensity significantly increased in ASODNs cotransfection SGC7901/ADM cells, compared with those transfected by MDR1 or MRP ASODNs respectively;In addition,the sensitivity of SGC7901/ADM cells to adriamycin, carboplatin and other anticancer drugs obviously increased after cotransfection of MDR1 and MRP ASODNs compared with transfection of MDR1 or MRP ASODN respectively. Conclusion:The transfection of MDR1 or MRP ASODN can partly reverse the multidrug resistance of gastric glandular carcinoma cells SGC7901/ADM,while cotransfection of MDR1 and MRP ASODNs can significantly reverse drug-resistance of these tumor cells.