中文摘要：

目的探讨雷帕霉素（RPM）与5-氮脱氧胞苷（5-aza-dC）对小鼠大肠癌的联合抑制作用及机制。方法应用二甲基肼（DMH）颈后皮下注射20周建立小鼠大肠癌模型。从第16周起给予RPM、5-aza-dC以及RPM＋5-aza-dC腹腔注射，共8周；至试验24周处死实验动物，测算肿瘤体积，以HE染色判断肿瘤发生率；应用免疫组织化学法（IHC）检测肿瘤组织mTOR、p70s6K、4E-BPI蛋白的磷酸化水平。结果RPM、5-aza-dC及RPM＋5-aza-dC干预组小鼠大肠癌发生率显著低于模型组；RPM及RPM＋5-aza—dC干预组肿瘤体积明显小于模型组；5-aza-dC干预组肿瘤组织的mTOR磷酸化水平，以及RPM干预组mTOR、p70s6K,4E-BPI蛋白磷酸化水平显著低于模型组。在降低肿瘤发生率、减小肿瘤体积以及抑制mTOR信号通路活性方面，RPM＋5-aza-dC作用组的效果显著优于RPM及5-aza-dC单独作用组。结论RPM与5-aza-dC可联合抑制小鼠大肠癌的发生和生长，其作用机制可能涉及对mTOR信号转导通路相关蛋白磷酸化水平的调控。

英文摘要：

Objective To evaluate the effect of rapamycin and 5-aza-dC combination therapy on mouse colon cancer and its potential mechanisms. Methods S-ICR mice were subcutaneously injected with 20 mg/kg 1,2-Dimethylhydrazine dihydrochloride （DMH） in the nape every week for 20 weeks to induce colon cancer. From the 16th week, the mice were treated with rapamyein or 5-aza-dC or both for 8 weeks, afterwards the animals were sacrificed and the tumor size was measured. The development of cancer was determined microscopically,and phosphorylation of mTOR, p70S6K, and 4E-BPI proteins were checked immunohistochemically. Results Both combination and single-drug treatments significantly decreased the incidence of colon cancer, and group of rapamycin or rapamycin plus 5aza-dC showed smaller tumor size. Phosphorylation level of mTOR in 5aza-dC group, and that of mTOR,p70s6K,4E-BPI proteins in RPM group were sig- nificantly lower than those of the control. While the effect of combination treatments of 5aza-dC plus RPM was remarkably superior to that of the single drug in decreasing the occurrence and size of tumor, and in suppressing the activity of mTOR pathway. Conclusion Combination treatment with 5-aza-dC and rapamycin decreased the incidence of colon cancer in mouse, and decreased tumor sizes. The mTOR signal pathway might be inhibitory mechanism.