Celecoxib通过β-catenin-Tcf/Lef通路诱导SW620细胞凋亡的体外研究  

Studies of Celecoxib on inducing apoptosis in SW620 human colon cancer cells through β-catenin-Tcf/Lef pathway in vitro

作　　者：刘锋[1] 张显玉[1] 何川[1] 刘扬[1] 董新舒[2] 

机构地区：[1]哈尔滨医科大学附属肿瘤医院乳腺外科,150081 [2]哈尔滨医科大学附属肿瘤医院结直肠外科,150081

出　　处：《国际遗传学杂志》2010年第6期321-325,共5页International Journal of Genetics

基　　金：黑龙汀省教育厅面上项日（11541175）;哈尔滨医科大学附属肿瘤医院院内基金（JJ2007-05）

摘　　要：目的 研究Celecoxib抗大肠癌的分子生物学机制.方法 不同浓度的Celecoxib作用于大肠癌细胞SW620,MTT（methyl thiazolyl tetrazolium,MTT）法检测细胞增殖,Western印迹检测β-catenin 和survivin蛋白表达的变化,流式细胞仪检测细胞凋亡的变化.siRNA沉默β-catenin,观察survivin蛋白表达变化情况.结果 Celecoxib浓度在10-mmol/L～10-3mmol/L范围内表现出较强的抑制细胞增殖的效应分别为34.13%、68.93%和71.66%,呈剂量依赖性;Celecoxib可抑制β-catenin和survivin蛋白表达;流式细胞仪检测结果显示60 μmol/L和80μmol/L Celecoxib处理后SW620细胞凋亡比例明显增高,凋亡细胞分别为对照组的4.9倍[（x±s）%=（4.02±0.67）%,P=0.007 837]和8.2倍[（x±s）%=（6.50±0.56）%,P=0.004 296];siRNA沉默β-catenin后发现survivin表达显著降低.结论 Celecoxib通过影响β-catenin,进一步通过β-catenin-Tcf/Lef途径抑制survivin表达来起到诱导SW620细胞凋亡的作用.Objective Investigate the antitumor mechanisms of Celecoxib on colon cancer. Methods The proliferation of SW620 cells treated with various concentration of Celecoxib was detected by MTT assay.The expression of β-catenin and survivin was tested by western blot assay. Flow cytometric assay （ FCM ） was used to detect apoptosis. The expression of survivin protein was detected by western blot assay after β-catenin expression was interfered by siRNA. Results We present here colon cancer cells proliferation was suppressed significantly compared with control group, when Celecoxib concentration was in the range of 10-5 mmol/L ～10-3mmol/L（34. 13% 、68. 93% and 71.66% ）. Thus, Celecoxib could inhibit cancer cells proliferation in a concentration-dependent manner. We found that the expression of β-catenin and survivin were suppressed by 60 μmol/L and 80 μ mol/L celecoxib treatment in SW620 cells in a concentration-dependent way. Moreover,the percentage of apoptosis cells was significantly higher than the control group （4. 9 and 8. 2 times compared to control group） by 60 μ mol/L and 80 μ mol/L Celecoxib treated in SW620 for 24 hours. The value of apoptotic index were respectively （4.02 ± 0. 67 ） % （ P = 0. 007 837 ） and （ 6. 50 ± 0. 56 ） % （ P = 0. 004 296 ）. Otherwise, the expression of survivin significantly decreased when siRNA interfered β-catenin. Conclusion We cofirmed that celecoxib inhibited survivin expression by the regulation of β-catenin expression through β-cateninTcf/Lef pathway and induced SW620 cells apoplosis.

关 键 词：大肠癌 CELECOXIB Β-CATENIN SURVIVIN 凋亡 

分 类 号：R735[医药卫生—肿瘤]