Ginsenoside Rh2 reverses P-glycoprotein-mediated multidrug resistance of MCF-7/ADM cells / 肿瘤

ABSTRACT

Objective: Multidrug resistance (MDR) of malignant tumors to chemotherapeutic agents has played a major role in the failure of cancer chemotherapy. Finding effective and low toxic reversing agents against MDR has been a critical challenge. In this study, we aim to investigate the reversing effects of ginsenoside Rh2 on MDR in vitro its the corresponding mechanism. Methods: MCF-7 or MCF-7/ADM cells were incubated with ginsenoside Rh2 alone or in combination with adriamycin (ADM), respectively. The viabilities of MCF-7 and MCF-7/ADM cells were assessed by MTT method and the in IC50 values were calculated. The inhibitory effects of Rh2 and verapamil on the efflux of rhodamine 123 were assayed by flow cytometric analysis. The expression of mdr1 gene was measured by RT-PCR and P-gp expression was determined by flow cytometry. Results: Ginsenoside Rh2 significantly decreased IC50 value of ADM on MCF/ADM cells (P <0.05), but it had no effect on MCF-7 cells. Rh2 and verapamil significantly increased the accumulation of rhodamine 123 in drug-resistant cells MCF - 7/ADM in a dose-dependent manner (P <0.05), but they had no effect on MCF-7 cells. Ginsenoside Rh2 had stronger effect in inhibition of rhdamine 123 efflux than verapamil. RT-PCR and flow cytometric analysis showed that the expressions of mdr1 gene and P-gp had no significant difference in MCF-7/ADM cells after ginsenoside Rh2 treatment. Conclusion: Ginsenoside Rh2 effectively reverses P-gp-mediated drug resistance of MCF-7/ADM cells.