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,16d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100mg.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35d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、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(P<0.05),各组COX-2、survivin和β-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。
Objective To study the effect of Wnt signal pathway on celecoxib against colon cancer. Methods Human colon cancer HT-29 ceils 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·d^-1）. 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 β- catenin 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 β-catenin were low （ all P 〈 0. 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 pathway dependent or independent on COX-2 and inducing cell apoptosis. Low doses of celecoxib is a better choice for the clinical treatment.
出处
《中国老年学杂志》
CAS
CSCD
北大核心
2009年第8期917-920,共4页
Chinese Journal of Gerontology
基金
河北省科技厅科技攻关项目(072761314)
