Reversal Effect Of Osthol On Adriamycin Resistance In Human Breast Cancer Cells

Objectives:To explore the inhibitory effects of osthol (Ost) on cancer cell lines through observing the influence of adriamycin(ADR) on growth of human breast cancer cell line (MCF-7) and adriamycin resistant MCF-7 (MCF-7/ADR). To explore the effects of Ost on sensitizing MCF-7 to chemotherapy in vitro by observing the influence of Ost for the cytotoxicity of ADR on MCF-7.To explore the reversive effect and its mechanism of Ost on the multidrug resistance(MDR) by observeing the effects of Ost for reverseing MDR and changing intracellular accumulation of ADR.Methods:1,MTT assay was used to evaluate the growth inhibitory of cytotoxicity,reverse effect of Ost on MCF-7 and MCF-7/ADR cells ;2,HPLC method with UV detection was used to determine intracellular concentration of ADR . The effect of Ost on intracellular concentration of ADR was compared with calcium channel inhibitory verapamil (Ver).Results:1,Osthol inhibituted the proliferation of MCF-7 and MCF-7/ADR with IC50 58.14±2.33μmol·L^-1and 59.20±4.54μmol·L^-1 respectively. The inhibitory rates were lower than 10% with contration of Ost in the range of 5-20μmol·L^-1 for MCF-7 and MCF-7/ADR cells;2,Ost enhanced lethal effect of ADR for MCF-7 cell within the contration of 5^-15μmol·L^-1 which showed no cytotoxicity ;3,Administration of Ost in the concentration of 5,10,15μmo l·L^-1 with significantly decreased the IC50 .Difference between the ethal effect of ADR puls Ost and that of ADR alone was significant((P<0.01) .The reversal fold for Ost of 5,10,15μmo l·L^-1 was 8.79,11.85,18.17 respectively ;4,Ost in the concentration of 5,10,15μmol·L^-1 significantly increased the intracellular concentration of ADR..It was a statistics significance as compared with ADR alone (P<0.01); Conclusions:Ost can inhibit proliferation of adriamycin human breast cancer cell line (MCF-7) and its adriamycin resistant human breast cancer cell line (MCF-7/ADR) . Ost with no cytotoxicity doses enhanced sensitization for chemotherapy drug in vitro and intracellular accumulation of adriamycin, reverse multidrug resistance in MCF-7/ADR cells.