环境浓度下DDT暴露对Wnt/β-catenin信号通路介导的大肠癌肿瘤学效应的影响

项目名称： 环境浓度下DDT暴露对Wnt/β-catenin信号通路介导的大肠癌肿瘤学效应的影响

项目编号： No.21207084

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 环境化学

项目作者： 宋莉

作者单位： 山西大学

项目金额： 25万元

中文摘要： 大肠癌是危害人民健康的常见恶性肿瘤之一，且Wnt/β-catenin信号通路激活在大肠癌进展中起决定性作用。流行病学调查发现大肠癌发生发展与DDT污染有关，但其分子机制尚不清楚。本项目前期研究表明，DDT暴露促进肠癌细胞增殖和迁移，且引起Wnt/β-catenin信号通路激活。在此基础上，本项目拟以p,p'-DDT为目标化合物，在大肠癌不同病理分期患者中分析Wnt/β-catenin信号通路异常激活和DDT污染特征与大肠癌的相关性；以肠癌裸鼠模型验证Wnt/β-catenin信号通路介导的DDT暴露对大肠癌发展的影响；以肠癌细胞系研究Wnt/β-catenin信号通路介导的DDT暴露促进肠癌细胞增殖及其引起大肠癌发展的分子机理。本项目旨在阐明环境浓度DDT暴露下，Wnt/β-catenin信号通路介导的大肠癌发展过程及其分子机制，为相关人群大肠癌预防和控制提供科学依据。

中文关键词： DDT暴露；Wnt/β-catenin信号通路；大肠癌；；

英文摘要： Colorectal cancer is one of the common malignant tumors, and Wnt/β-catenin signaling pathway lays a crucial role in the colorectal carcinogenesis. Epidemiological surveys discovered that colorectal cancer occurrence and development are related to DDT pollution, but its molecular mechanism remains unclear. Our previous studies indicated that DDT exposure promotes cancer cell proliferation and migration, and causes the Wnt/β-catenin signaling pathway activation. On this basis, this project intends to use p, p'-DDT as a target compound. We are firstly going to measure DDT concentrations in serum and the expression levels of Wnt signaling molecules in the colorectal cancer patients with different pathological staging. Combined with pathological staging, we shall analyze the relevance of Wnt/β-catenin signal pathway abnormal activation、 pollution characteristics of DDT with the incidence of colorectal cancer. Moreover, we are going to use the nude mice colorectal cancer model to validate the influences of Wnt/β-catenin signaling pathway mediated by DDT exposure on colorectal carcinogenesis. On this basis, the cancer cell lines will be hired to study the molecular mechanism of Wnt/β-catenin signaling pathway mediated by DDT exposure on colorectal carcinogenesis. This project aims to elucidate the molecular mechanisms

英文关键词： DDT exposure；Wnt/β-catenin signaling pathway；Colorectal cancer；；