Effect Of The Function Of MRP1 On Human Lung Adenocarcinoma Chemotherapy Resistance

Objective: To investigate the effect of MRP inhibitor MK-571 on the function of MRP1 in A549/DDP and A549, two different histological subtype cell lines of lung adenocarcinoma, and the survival rates of the two subtype cells treated by cisplatin chemotherapy,and find the effect of the function of MRP1 on human lung adenocarcinoma against chemotherapy resistance.Methods: A549/DDP and A549 two cell lines which were in good condition were randomly divided into two groups, experimental group and control group. The experimental group cells were treated with MK-571 for 24 hours. The expression of MRP1 at mRNA level in all groups was detected by RT-PCR. Using the Rh123 dyeing method to test the pump function of MRP. Survival rates of cells against cisplatin were detected by the colorimetric MTT assay and calculated the value of IC50.Results: 1. There is no significant difference between A549/DDP and A549 cell lines for the expression of MRP1 mRNA (p>0.05). 2. The function of MRP1 detected by Rh123 dyeing method indicated that the fluorescence intensity of experimental group of A549/DDP and A549 two cell lines was stronger than the control. Also there was a dose-dependent manner of MK-571 to the fluorescence intensity of experimental group. All of these indicated that MK-571 inhibited the function of MRP1. 3. Cell viability was examined by MTT assay and the IC50 values for cisplatin was calculated. The IC50 value of MK571-treated cells for cisplatin was lower than that of the control cells in both A549/DDP and A549 two cell lines. The sensitivity of experimental group of two cell lines to cisplatin significantly increased compare to the control (P < 0.05).Conclusion: Our research showed in the following.1.MK-571 can not inhibit the MRP1 mRNA expression of A549/DDP and A549 cell lines.2.MK-571 can inhibit the function of MRP1.3.MK-571 can increase the sensitivity of A549/DDP and A549 cell lines to cisplatin through inhibiting the function of MRP1. Our research provided a approach of reversal chemoresistance.