TWS119对结肠癌LOVO细胞系增殖能力和耐药性的影响.docVIP

TWS119对结肠癌LOVO细胞系增殖能力和耐药性的影响 [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2 μmol/L TWS119处理组、1 μmol/L TWS119处理组和阴性对照组，TWS119处理组加入2、1 μmol/L的TWS119，对照组加入等体积DMSO，培养24 h后分别进行Western blot和qRT-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，2 μmol/L TWS119处理组和1 μmol/L TWS119处理组细胞中MRP1、P-gp的mRNA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），但2 μmol/L TWS119处理组存活率明显升高（P 0.05）；而且在15 μmol/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。 [关键词] 结直肠癌；化疗耐药；TWS119；Wnt/β-catenin信号通路 [中图分类号] R73-36 [文献标识码] A [文章编号] 1673-7210（2015）09（a）-0027-05 [Abstract] Objective To discuss 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， 1 μmol/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 G2/M period cell rate in 2 μmol/L TWS119 treatment group and 1 μmol/L TWS119 treatment group significantly increased （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 res