分化抑制因子家族调控结直肠癌侵袭转移机制的研究

项目名称： 分化抑制因子家族调控结直肠癌侵袭转移机制的研究

项目编号： No.81472720

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 叶韵斌

作者单位： 福建省肿瘤医院

项目金额： 64万元

中文摘要： 分化抑制因子（Inhibitors of differentiation, Id）作为新的肿瘤相关基因在一些癌症包括结直肠癌中高表达，并被证明具有促进肿瘤生长、侵袭和转移的作用，并维持胚胎干细胞自我更新的功能。肝转移是肠癌治疗中棘手的问题之一，其机理并不明确。虽有少量的研究表明Id分子具有促进早期血行播散和调节肿瘤干细胞的自我更新的作用，但其在肠癌肝转移以及维持肠癌干细胞相关特性作用需要进一步验证。本研究采用基因转染技术提高或减低肠上皮细胞和肠癌细胞Id分子表达，通过体外细胞学和分子生物学实验，研究Id对肠癌细胞侵袭能力的影响以及相关的分子机制。进一步建立盲肠原位移植肠癌肝转移的裸鼠模型，通过分析肠癌细胞在体内的侵袭转移规律，探索Id分子对于肠癌肝转移调控的机制，从而为肠癌肝转移的治疗提供新的思路。

中文关键词： C08_结；直肠肿瘤；肿瘤转移；上皮间质转化；间质上皮转化

英文摘要： Inhibitor of differentiation (Id) families are overexpressed in several kinds of cancer including colorectal cancer. Ids have been shown to promote tumor growth, invasion and metastasis, and maintenance the embryonic stem cell self-renewal function. Liver metastasis is one of the difficult problems in the therapy of colorectal cancer, in which the mechanism is not yet clear. Although a small amount of researchs have shown that Id can promote the early hematogenous dissemination，and regulate the self-renewal of cancer stem cells, it needs the further verification about the role of Ids on the hepatic metastasis of colorectal carcinoma and the colorectal cancer stem cells characteristics. In this study, we will use gene transfection technique to increase or decrease Ids expression in intestinal epithelial cells and several kinds of colorectal cancer cell lines, and study the effects of Ids on invasion and metastasis of colorectal cancer by cytobiological and molecular biological experiments, as well as analyze the detail molecular mechanisms. Furhtermore we will establish an orthotopic colorectal cancer liver metastasis animal model by inoculating colorectal cancer cell into the cecum of the nude mice, and explore the mechanism of Ids in controllong the metastasis in vivo. All the data would provide new ideas for the therapy of liver metastases from colorectal cancer.

英文关键词： colorectal cancer;cancer metastasis;EMT;MET