Effects Of Rosiglitazone On The Drug-resistant Breast Cancer Cell

Objective To investigate the proliferation inhibition and the reverse effects as well as the mechanisms of rosiglitazone(ROS) on human breast cancer cells resistant to tamoxifen(MCF-7/TAM).Methods ROS of various concentrations(0、50、100、150、200、250 μmol/L)was used to intervene MCF-7/TAM cells in vitro. The effects of ROS on cell proliferation was then assessed by MTT assay at the time point of 24 h, 48 h and72 h. The rate of apoptosis induced by ROS was determined at the time point of48 h with flow cytometry. TAM of various concentrations(0.1、1、10、20、40μmol/L) was used to intervene MCF-7 cells 、 MCF-7/TAM cells and MCF-7/TAM cells treated with ROS(136 μmol/L) for 48 h in vitro. The effects of TAM on cell proliferations were then assessed by MTT assay at the time point of48 h.The expression changes of FOXA1,ERa,Erb B-2 and P53 of MCF-7/TAM cells which dealed with ROS were detected by real-time fluorescence quantitative PCR.Results 1.Different concentrations of ROS(0、50、100、150、200、250μmol/L) were applied to MCF-7/ TAM cells for 24 h, 48 h and 72 h, the proliferation inhibition rate rase from 14.2% to 62.1% at the time point of 24 h.The inhibitory rate rase from 21.7% to 64.4% at the time point of 48 h. The inhibition rate rase from 33.7% to 74.4% at the time point of 72 h.The inhibitoryeffect of ROS on MCF-7/TAM cells was positively correlated with the concentration and time.2.TAM of various concentrations(0.1、1、10、20、40μmol/L) was used to intervene MCF-7 cells 、MCF-7/TAM cells and MCF-7/TAM cells treated with ROS(136 μmol/L) for 48 h in vitro.The uumber of IC50 were(6.81 ± 0.02)μmol/L 、(17.92 ± 0.03) μmol/L and(8.76 ± 0.01) μmol/L respectively.The multidrug resistance was 2.63(t=51.20, P<0.05), and the reversal of drug resistance was 2.05(t=65.32, P<0.05).3.ROS of various concentrations(150、200、250 μmol/L)was treated to MCF-7/ TAM cells for 48 h, the cell apoptosis rate were(16.20±0.30)%、(22.53±0.15)% and(27.53±0.35)% respectively.Compared with the control group(3.23 ± 0.04)%, the apoptosis rate was increased(F=5559, P<0.05).4.The expression of FOXA1,ERa and P53 were increased(P<0.05)after ROS effected on MCF-7/TAM cells at the dose of 50% inhibitory concentration(136 μmol/L).While,the expressions of Erb B-2 were induced(P<0.05) by ROS with the same concentration.Conclusion The effects of proliferation inhibition and apoptosis of ROS more than 50μmol/L on MCF-7/TAM cells may be related to down-regulating P53 expression.ROS can reverse the drug resistance of MCF-7/TAM cells,and the reverse mechanisms maybe relate to up-regulating FOXA1 and ERa expression as well as down-regulating Erb B-2 at the dose of 50% inhibitory concentration(136 μmol/L).