THE EFFECT OF IRISQUINONE ON THE GLUTATHIONE SYSTEM AND MRP EXPRESSION OF CISPLATIN-RESISTANTHUMAN LUNG ADENOCARCINOMA CELL LINE (A549DDP)

摘要

Objective: To investigate the Reversal Effect of Irisquinone （ANKA） on Cisplatin-resistant Human Lung Adenocarcinoma Cell Line (A549DDP) and the change of MRP expression. Methods: MTT assay, flow cytometry, glutathione reductase recycling assay, RT-PCR were used. Results: None or low cytotoxic concentration of ANKA (10, 20, 30 （mol/L） could increase the sensitivity of A549DDP cells to CDDP by 8.2, 7.9 and 8.9-fold in a dose independent manner. After A549DDP cells was pretreated with 10 (mol/L ANKA for 12 h, CDDP cytotoxicity was increased 9.41-fold. The GSH content of the cells treated by ANKA is reduced significantly （P<0.001）. The GST( protein expression was reduced by ANKA depended on its doses. ANKA also reduced expression of MRP protein, dependent on its dose and treating time （P<0.001）. MRP mRNA expression was reduced only by 30 (mol/L ANKA （P<0.05）. Conclusion: The reversal effect of ANKA on A549DDP cell was relative to intracellular glutathione system.