人参皂甙Rh2逆转P-gp介导的MCF-7/ADM多药耐药性的基础研究

目的：研究人参皂甙Rh：在逆转多药耐药（MDR）方面的作用及其机理。方法：Rh：和阿霉素单独或联合作用于MCF-7及MCF-7／ADM细胞，应用MTT法确定各组细胞的IC50。罗丹明123加入各组细胞，流式细胞仪分析Rh2和维拉帕米抑制罗丹明123外排的情况。RT—PCR检测各组mdrl mRNA表达量及流式细胞仪检测各组P—gP的表达情况。结果：Rh2可以显著降低MCF-7／ADM的ADM IC50（P〈0．05），对MCF-7细胞没有影响。Rh2和维拉帕米可以增加MCF-7／ADM细胞内罗丹明123荧光表达率（P〈0．05），Rh3比维拉帕米抑制罗丹明123外排作用更强。在MCF-7细胞内Rh2和维拉帕米无此作用。Rh2对MCF-7／ADM细胞mdrl mRNA表达及P—gP表达没有影响。结论：人参皂甙Rh2可以有效逆转P—gP介导的人乳腺癌细胞耐药细胞系MCF-7／ADM的耐药性。

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

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-gpmediated drug resistance of MCF-7/ADM cells.