Wnt信号传导通路在塞来昔布抗结肠癌生长中的作用..docVIP

Wnt信号传导通路在塞来昔布抗结肠癌生长中的作用 ：赵士彭蔡建辉赵发徐德龙卞红磊张燕 桂林 】目的研宄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榴水，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C0X 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P连接素（P catenin）蛋白 的表达。结果低、中和高剂量塞来昔布组的抑瘤率分别为34. 94%、39. 20% 和59. 20%,与对照组比较，塞来昔布各组移植瘤体积明显缩小（P0. 05）， 各组COX 2、survivin和P catenin蛋白表达水平均明显降低（均P 0.05）。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； 0连接素；细 胞凋亡 [Abstract] Objective To study the effect of Wnt signal pathway on celecoxib against colon cancer. Methods Human colon cancer HT 29 cells were injected into the BALB/c nude mice back subcutaneously to establish transplantable tumor model. After 16 days, mice were randomly divided into control group and, low, middle and high dose celecoxib groups (25, 50 and 100 mg ? kg-1 e d~l). Mice were given sterilized distilled water and different doses of celecoxib in control and different celecoxib groups respectively. The expression of COX 2 protein was measured by immunohistochemistry method, apoptotic cell was detected by TUNEL, and apoptosis inhibition protein survivin and 0 catcnin protein were examined by Western blot in carcinomic tissue.Results The inhibition rate of low, middle and high dose of celecoxib was 34. 94%, 39.20% and 59.20% respectively. Compared with control group, the volumes of transplantable tumor of three dose of celecoxib groups were all small (all P 0. 05), and the expressions of COX 2, survivin, and 3 catenin were low (all P0. 05). The effect of celecoxib on tumor growth, cell apoptosis, and the expressions of COX 2 and survivin turned large with the increasing of dose. Conclusions Celecoxib can suppress tumour growth in different dose and the inhibition effect has obvious dose dependence ， which come true by inhibiting Wnt signal pa