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  

Curcumin reversal multidrug resistance through downregulation of STAT3 signaling in colon cancer cell lines resistant to oxaliplatin

作　　者：文坤明[1] 冷敏[1] 程家平[1] 陈正权[1] 陈奕霖[1] 曾庆良[1] 

机构地区：[1]遵义医学院附属医院胃肠外科,遵义563003

出　　处：《中国免疫学杂志》2015年第8期1056-1059,共4页Chinese Journal of Immunology

基　　金：国家自然科学基金资助项目(No.81260369);贵州省科技厅科学技术基金[黔科合(J)字LKZ(2013)50号]

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 for48 h,while in the control group,SW620 / OxR cell lines were cultured in medium containing in 2 μmol / 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（ PSTAT3） 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.

关 键 词：结直肠癌 多药耐药 姜黄素 STAT3信号通路 

分 类 号：R735.35[医药卫生—肿瘤]