The effect of Irisquinone on the glutathione system and MRP expression of cisplatin-resistant human lung adenocarcinoma cell line (A 549 DDP )

Objective: To investigate the Reversal Effect of Irisquinone (ANKA) on Cisplatin-resistant Human Lung Adenocarcinoma Cell Line (A ₅₄₉ ^DDP ) 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 μmol/L) could increase the sensitivity of A ₅₄₉ ^DDP cells to CDDP by 8.2, 7.9 and 8.9-fold in a dose independent manner. After A ₅₄₉ ^DDP cells was pretreated with 10 μmol/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 GSTπ 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 30μmol/L ANKA (P<0.05). Conclusion: The reversal effect of ANKA on A ₅₄₉ ^DDP cell was relative to intracellular glutathione system. Foundation item: This work was supported by the grant from the National 9th five-year program for Scientific Research of China (96-906-01-23). Biography: LIANG li (1967-), master of medicine, now works at the Department of Tumor, Peking University Third Hospital, majors in oncology.