IL-1β通过NF-κB/Lipocalin2调控大肠癌上皮间质转化的机制研究

项目名称： IL-1β通过NF-κB/Lipocalin2调控大肠癌上皮间质转化的机制研究

项目编号： No.81472215

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： 徐芳英

作者单位： 浙江大学

项目金额： 72万元

中文摘要： 转移是大肠癌患者死亡的最主要原因，上皮间质转化（EMT）是转移发生的重要机制，涉及多种分子和信号通路。炎症因子IL-1β主要是由单核巨噬细胞或内皮细胞分泌产生，可以通过激活肿瘤细胞内的NF-κB上调Lipocalin2（LCN2）的表达。前期实验结果初步发现在大肠癌中，IL-1β可以激活NF-κB、抑制E-cadherin表达、上调Snail，还能促进LCN2表达；NF-κB可以促进EMT，LCN2却抑制EMT。因此本课题拟通过体外细胞系实验、体内动物实验及人体组织样本检测，明确IL-1β是否可以通过激活NF-κB来促进EMT，其上调的LCN2是否能抑制IL-1β/NF-κB引起的EMT，形成负反馈性调控。从而为阐明炎症微环境与肿瘤转移之间的调控机制提供新思路。

中文关键词： IL-1β；NF-κB；lipocalin2；大肠癌；上皮间质转化

英文摘要： Metastasis is the main cause of death in patients with colorectal cancer. Epithelial mesenchymal transition (EMT), which is the important mechanism in metastasis, involves a variety of molecules and signaling pathways. Inflammatory cytokines IL-1β, mainly produced by monocytes, macrophages and endothelial cells, can upregulate the expression of lipocalin2(LCN2) by active NF-κB. In previous study, our group found that IL-1βactivated NF-κB , inhibited the expression of E-cadherin, and upregulated the expression of Snail and LCN2. Moreover, the results showed that NF-κB promoted EMT, and LCN2 inhibited EMT. In this study, we will clarify whether IL-1β can induce EMT by the activation of NF-κB, and whether the upregulation of LCN2 can inhibit EMT induced by IL-1β/NF-κB pathway. The experimental methods include in vitro experiments in cell lines, in vivo animal experiments, and detection in tissue samples. It will provide a theory model on the relation between tumor inflammatory microenvironment and metastasis.

英文关键词： IL-1β;NF-κB;lipocalin2;colorectal cancer;epithelial mesenchymal transition