Wnt信号传导通路在塞来昔布抗结肠癌生长中的作用.doc

文档介绍：Wnt信号传导通路在塞来昔布抗结肠癌生长中的作用
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作者:赵士彭蔡建辉赵发徐德龙卞红磊张燕桂林
【摘要】目的研究Wnt信号传导通路在塞来昔布抗结肠癌生长中的作用。方法将人结肠癌HT29细胞注射于裸鼠背部皮下建立移植瘤模型,16 d后,将裸鼠随机分为对照组、低、中和高剂量塞来昔布组(25、50和100 mg·kg-1·d-1),对照组灌胃给予灭菌蒸馏水,各塞来昔布组给予相应剂量的塞来昔布。给药35 d后,以免疫组织化学方法检测瘤组织COX2蛋白表达,以TUNEL方法检测细胞凋亡,以Western印迹方法检测凋亡抑制蛋白生存素(survivin)和β连接素(βcatenin)蛋白的表达。结果低、%、%%,与对照组比较,塞来昔布各组移植瘤体积明显缩小(P<),各组COX2、survivin和βcatenin蛋白表达水平均明显降低(均P<)。塞来昔布对肿瘤生长、细胞凋亡、COX2和survivin表达的影响程度随用药剂量的增加而增强。结论不同剂量的塞来昔布均能明显抑制结肠癌移植瘤的生长,其抑制作用呈明显的剂量依赖性,这种作用是通过COX
2依赖或非依赖途径对Wnt信号通路的抑制来诱导细胞凋亡实现的。低剂量塞来昔布是临床治疗的较好选择。
【关键词】结肠癌;环氧化酶2抑制剂;survivin;β连接素;细胞凋亡
【Abstract】 Objective To study the effect of Wnt signal pathway on celecoxib against colon Human colon cancer HT29 cells were injected into the BALB/c nude mice back subcutaneously to establish transplantable tumor 16 days,mice were randomly divided into control group and,low,middle and high dose celecoxib groups (25,50 and 100 mg·kg-1·d-1).Mice were given sterilized distilled water and different doses of celecoxib in control and different celecoxib groups expression of COX2 protein was measured by immunohistochemistry method,apoptotic cell was detected by TUNEL,and apoptosis inhibition protein survivin and βcatenin protein were examined by Western blot in carcinomic The inhibition rate of low,middle and high dose of celecoxib was %,% and % pared with control group,the volumes of transplantable tumor of three dose of celecoxib groups were all small(all P<),and the expressions of COX
2,survivin,and βcatenin were low (all P<).The effect of celecoxib on tumor growth,cell apoptosis,and the expressions of COX2 and survivin turned large with the increasing of Celecoxib can suppress tumour growth in different dose and the inhibition effect has obvious dosedependence,e true by inhibiting Wnt signal pathway dependent or i