姜黄素通过抑制STAT3通路调控人结肠癌耐奥沙利铂细胞株的耐药性

摘要

目的：：探讨姜黄素( Cur）对人结肠癌耐奥沙利铂( Oxa）细胞株( SW620／OxR）的逆转耐药作用及其机制是否与抑制STAT3信号通路有关。方法：采用WST-1试剂检测Cur对SW620／OxR细胞株的半数抑制( IC50）浓度，选择IC50低一浓度梯度的Cur＋2μmol／L Oxa作用于SW620／OxR细胞48 h(称为实验组），与仅加入2μmol／L的Oxa对照组比较，①采用流式细胞术检测细胞凋亡；②采用Western blot检测STAT3活化标志磷酸化STAT3( P-STAT3）蛋白及其下游耐药相关靶分子P糖蛋白( P-gp）的表达情况。结果：Cur对SW620／OxR细胞的IC50浓度为18.9μmol／L；实验组与对照组比较：①细胞凋亡率由(5.08±1.82）％上升到(30.69±2.94）％，实验组细胞凋亡率明显高于对照组(P＜0.05）；②P-STAT3及P-gp表达量均明显受抑制( P＜0.05）。结论：Cur具有调控人结肠癌耐药细胞株耐药性的作用，可能与抑制STAT3信号通路，降低P-gp表达有关。%Objective:To investigate the reversal multidrug resistance effects of curcumin on human colorectal cancer cell lines resistant to oxaliplatin( SW620/OxR) and whether its mechanism was involved in downregulation of STAT3 signaling.Methods: The IC50 value(50%cell growth inhibitory concentrations) of curcumin to SW620/OxR cell lines was obtained by WST-1 reagent,which was one kind of cell proliferation assay.Later experiments included in the experimental group and the control group.In the experimental group,SW620/OxR cell lines were exposed to the previous experiment IC50 concentrations of curcumin plus 2 μmol/L oxaliplatin for 48 h,while in the control group,SW620/OxR cell lines were cultured in medium containing in 2μmol/L oxaliplatin.In the two groups:apoptosis was detected by flow cytometry;the protein expression levels of phosphorylated STAT3(P-STAT3) and P-gp were disclosed by Western blot.Results:The IC50 value of curcumin to SW620/OxR cell lines was 18.9 μmol/L.The apoptosis rate of cells in the control group and the experimental group were respectively ( 5.08 ±1.82 )% and ( 30.69 ±2.94 )%, the apoptosis rate of the experimental group was significantly higher than that of the control group ( P<0.05 ) .The protein expression levels of phosphorylated STAT3(P-STAT3) and P-gp in the experimental group was significantly lower than that in the control group(P<0.05).Conclusion:Curcumin can reverse drug resistance in colorectal cancer cell lines resistant to oxaliplatin, its effect may be associated with downregulation of STAT3 signaling pathways.