Imatinib and Nilotinib Reverse Multidrug Resistance in Cancer Cells by Inhibiting the Efflux Activity of the MRP7 (ABCC10)

• DOI: 10.1371/journal.pone.0007520
• Publication Date: 2009-10-19T21:12:27Z
• Authors: Tong Shen; Ye-Hong Kuang; Charles R. Ashby; Yu Lei; Angel Chen; Ying Zhou; Xiang Chen; Amit K. Tiwari; Elizabeth Hopper-...; Jiangyong Ouyang; Zhe-Sheng Chen
• Keywords: Efflux; Abcg2; HEK 293 cells; Imatinib Mesylate; MTT assay

One of the major mechanisms that could produce resistance to antineoplastic drugs in cancer cells is ATP binding cassette (ABC) transporters. The ABC transporters can significantly decrease intracellular concentration by increasing their efflux, thereby lowering cytotoxic activity drugs. these transporters, multiple resistant protein 7 (MRP7, ABCC10), has recently been shown efflux paclitaxel. In this study, we examined effects BCR-Abl tyrosine kinase inhibitors imatinib, nilotinib and dasatinib on expression MRP7 HEK293 transfected with MRP7, designated HEK-MRP7-2.We report for first time imatinib reversed MRP7-mediated multidrug resistance. Our MTT assay results indicated HEK-MRP7-2 was not altered incubation 5 microM or up 72 hours. addition, (1-5 microM) produced a significant concentration-dependent reversal enhancing sensitivity paclitaxel vincristine. Imatinib nilotinib, at microM, increased accumulation [(3)H]-paclitaxel cells. (5 also inhibited paclitaxel.Imatinib reverse resistance, most likely due inhibition via MRP7. These findings suggest combination other drugs, may be useful treatment certain cancers.