Reversal of Multidrug Resistance by Neferine in Adriamycin Resistant Human Breast Cancer Cell Line MCF-7/ADM

Abstract

Objective: To study the reversal effect of neferine on adriamycin (ADM) resistant human breast cancer cell line MCF-7/ADM. Methods: The cytotoxic effect of Nef or ADM was determined by 3-[4, 5-dimethylthiazol-2.-yl], 5-diphenyl tetraxolium bromid (MTT) assay. Apoptosis and the expression of P-glycoprotein (P-gp) were detected by flow cytometry (FCM). The intracellular ADM concentration was measured by HPLC. Results: Nef at 1, 5, 10 μmol/L decreased the IC50 of ADM to MCF-7/ADM from 11.63 μg/mL to 4.59, 2.44, 0.27 μg/mL respectively. MCF-7/ADM could resist the apoptosis induced by ADM while Nef (1-10 μmol/L) could augment ADR-mediated apoptosis. Nef (10 μmol/L) increased the accumulation of ADM up to 2.88 fold in MCF-7/ADM but not in sensitive cells MCF-7/S and reduced the expression of P-gp in MCF-7/ADM cells. Conclusion: Nef can circumvent multidrug resistance (MDR) of MCF-7/ADM cells and the mechanism was associated with the increase of intracellular accumulation of ADM and the reduced expression of P-gp in MCF-7/ADM cells.