TWS119对结肠癌LOVO细胞系增殖能力和耐药性的影响  

Impact of TWS119 on proliferation capacity and chemotherapy resistance of colon cell line LOVO

作　　者：冯家豪[1] 杨伟金 孙政[1] 

机构地区：[1]广州市第一人民医院胃肠外科,广东广州510180

出　　处：《中国医药导报》2015年第25期27-30,35,共5页China Medical Herald

摘　　要：目的探讨TWS119对结肠癌LOVO细胞系的耐药性和增殖能力的影响。方法将LOVO细胞系分成3组,分别为2μmol/L TWS119处理组、1μmol/L TWS119处理组和阴性对照组,TWS119处理组加入2、1μmol/L的TWS119,对照组加入等体积DMSO,培养24 h后分别进行Western blot和q RT-PCR检测β-链蛋白(β-catenin)多药耐药相关蛋白1(MRP1)及P糖蛋白(P-gp)的表达,用流式细胞分析检测细胞周期,用CCK8检测细胞耐药性变化。结果与阴性对照组比较,2μmol/L TWS119处理组和1μmol/L TWS119处理组细胞中MRP1、P-gp的m RNA和β-catenin、MRP1、P-gp的蛋白表达,G2/M期细胞比例均明显升高(P<0.05)。虽然1μmol/L TWS119处理组在5、10μmol/L5-氟尿嘧啶(5-Fu)作用下存活率无明显变化(P>0.05),但2μmol/L TWS119处理组存活率明显升高(P<0.05);而且在15μmol/L 5-FU作用下处理组存活率明显升高(P<0.05)。结论在体外实验中,TWS119可以通过上调Wnt/β-catenin信号通路活性增强结肠癌细胞的耐药性和增殖能力,揭示癌细胞耐药性、Wnt/β-catenin通路和ABC转运体如P-gp、MRP1等存在联系。Objective To discuse the impact of TWS119 on chemotherapy drug resistance and proliferation capacity of colon cancer cell line LOVO. Methods The cell line Lovo was divided into three group, 2 μmol/L TWS119 treatment group, 1μmol/L TWS119 treatment group and negative control group, the TWS119 treatment grouPs were added 2, 1 μmol/L TWS119, the negative control group was added equal volume of DMSO, Western blot and qRT-PCR were performed to test the expression of P-gp, β-catenin and MRP1 after 24 h treatment. Flow cytometry and CCK8 test were performed to analyze the cells tolerance change. Results Compared with the negative control group, the mRNA expression of MRP1, P-gp, the protein expression of P-gp, β-catenin and MRP1, the GJM period cell rate in 2 μmol/L TWS119 treatment group and 1 μmol/L TWS119 treatment group significantly increased （P 〈 0.05）; the survival rate with 5, 10 μmol/L 5-FU treatment had no significantly changed in 1 μmol/L TWS119 treatment group （P 〉 0.05）, while those in 2 μmol/L treatment group significantly increased （P 〈 0.05）, and the survival rate of both treatment group significantly increased with 15 μmol/L 5-FU treatment （P 〈 0.05）. Conclusion TWS119 can improve the chemotherapy drug resistance and proliferation capacity of colon cancer cell through increasing Wnt/β-catenin signaling pathway in vitro, these phenomena perhaps reveals there are some relationships among drug resistance of cancer cell, Wnt/β-catenin signaling pathway and the ABC transporter such as MRP1 and P-gp.

关 键 词：结直肠癌 化疗耐药 TWS119 WNT/Β-CATENIN信号通路 

分 类 号：R73-36[医药卫生—肿瘤]