中国医药导报
中國醫藥導報
중국의약도보
China Medical Herald
2015年
25期
27-30,35
,共5页
结直肠癌%化疗耐药%TWS119%Wnt/β-catenin信号通路
結直腸癌%化療耐藥%TWS119%Wnt/β-catenin信號通路
결직장암%화료내약%TWS119%Wnt/β-catenin신호통로
Colorectal cancer%Chemotherapy re-sistance%TWS119%Wnt/β-catenin
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，2μmol/L TWS119处理组和1μmol/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)。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。
目的：探討TWS119對結腸癌LOVO細胞繫的耐藥性和增殖能力的影響。方法將LOVO細胞繫分成3組，分彆為2μmol/L TWS119處理組、1μmol/L TWS119處理組和陰性對照組，TWS119處理組加入2、1μmol/L的TWS119，對照組加入等體積DMSO，培養24 h後分彆進行Western blot和qRT-PCR檢測β-鏈蛋白(β-catenin)多藥耐藥相關蛋白1(MRP1)及P糖蛋白(P-gp)的錶達，用流式細胞分析檢測細胞週期，用CCK8檢測細胞耐藥性變化。結果與陰性對照組比較，2μmol/L TWS119處理組和1μmol/L TWS119處理組細胞中MRP1、P-gp的mRNA和β-catenin、MRP1、P-gp的蛋白錶達，G2/M期細胞比例均明顯升高(P<0.05)。雖然1μmol/L TWS119處理組在5、10μmol/L5-氟尿嘧啶(5-Fu)作用下存活率無明顯變化(P>0.05)，但2μmol/L TWS119處理組存活率明顯升高(P<0.05)；而且在15μmol/L 5-FU作用下處理組存活率明顯升高(P<0.05)。結論在體外實驗中，TWS119可以通過上調Wnt/β-catenin信號通路活性增彊結腸癌細胞的耐藥性和增殖能力，揭示癌細胞耐藥性、Wnt/β-catenin通路和ABC轉運體如P-gp、MRP1等存在聯繫。
목적：탐토TWS119대결장암LOVO세포계적내약성화증식능력적영향。방법장LOVO세포계분성3조，분별위2μmol/L TWS119처리조、1μmol/L TWS119처리조화음성대조조，TWS119처리조가입2、1μmol/L적TWS119，대조조가입등체적DMSO，배양24 h후분별진행Western blot화qRT-PCR검측β-련단백(β-catenin)다약내약상관단백1(MRP1)급P당단백(P-gp)적표체，용류식세포분석검측세포주기，용CCK8검측세포내약성변화。결과여음성대조조비교，2μmol/L TWS119처리조화1μmol/L TWS119처리조세포중MRP1、P-gp적mRNA화β-catenin、MRP1、P-gp적단백표체，G2/M기세포비례균명현승고(P<0.05)。수연1μmol/L TWS119처리조재5、10μmol/L5-불뇨밀정(5-Fu)작용하존활솔무명현변화(P>0.05)，단2μmol/L TWS119처리조존활솔명현승고(P<0.05)；이차재15μmol/L 5-FU작용하처리조존활솔명현승고(P<0.05)。결론재체외실험중，TWS119가이통과상조Wnt/β-catenin신호통로활성증강결장암세포적내약성화증식능력，게시암세포내약성、Wnt/β-catenin통로화ABC전운체여P-gp、MRP1등존재련계。
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 2μmol/L TWS119 treatment group and 1 μmol/L TWS119 treatment group significantly increased (P< 0.05); the survival rate with 5, 10μmol/L 5-FU treatment had no significantly changed in 1μmol/L TWS119 treatment group (P>0.05), while those in 2μmol/L treatment group significantly increased (P<0.05), and the survival rate of both treatment group sig-nificantly 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 v itro, 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.
