炎症因子cathelicidin促进非小细胞肺癌增殖的作用及其在肿瘤微环境中表达调控机制

项目名称： 炎症因子cathelicidin促进非小细胞肺癌增殖的作用及其在肿瘤微环境中表达调控机制

项目编号： No.81472179

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： 李冬

作者单位： 同济大学

项目金额： 75万元

中文摘要： 我们前期研究发现，肿瘤微环境中炎症细胞分泌的炎症因子cathelicidin（Cath）是一个重要的肺癌生长因子，但是研究采用的小鼠肺癌模型为尾静脉肿瘤细胞注射法建立，有一定的局限性，同时对其促进肺癌增殖的作用机制还较少涉及，并且对其在肿瘤微环境中的表达调控机制还不清楚。为此，本研究拟以Cath敲除的非小细胞肺癌（NSCLC） 转基因小鼠模型（K-rasG12D；CRAMP-/-）为研究对象，研究Cath对NSCLC生长的影响；随后借助芯片、Western Blot技术检测肺癌细胞增殖信号等重要信号分子和信号转导通路的表达与活化；进而利用ChIP，CO-IP，荧光素酶报告基因，荧光共定位等细胞和分子生物学技术研究Cath促进NSCLC增殖的分子机制；最后明确Cath在肿瘤微环境中的表达调控机制。为阐明炎症因子Cath的表达调控及促进肺癌增殖的作用、机制与今后的应用价值提供实验依据。

中文关键词： cathelicidin；非小细胞肺癌(NSCLC)；细胞增殖；信号通路；表达调控

英文摘要： Although we previously reported the inflammatory factor cathelicidin（Cath）which secreted by inflammatory cells in the tumor microenvironment was an important growth factor for lung cancer, there are certain limitations including the generation of lung cancer model by tail vein injection of tumor cells into mice; the mechanism of Cath-induced proliferation of lung cancer is less involved; the expression regulation mechanism of Cath in the tumor microenvironment remain poorly understood. First of all this study is to investigate tumor growth promotion function of Cath in NSCLC transgenic mice with Cath knockout (K-rasG12D；CRAMP-/- mice); and then to analyze expression and activation of several important signaling molecules and signaling pathways such as proliferative signaling in tumor cells through chips and western blot; moreover, to research the molecular mechanisms of tumor promotion effect of Cath in NSCLC cells via cellular and molecular biology techniques containing CHIP, CO-IP, Luciferase reportor assay, and colocalization etc; finally, to confirm the expression regulation mechanism of Cath in the tumor microenvironment. This study will afford experiemental basis to elucidate the regulation of Cath and its effect, mechanism, and applied value in promoting proliferation of lung tumor.

英文关键词： cathelicidin;non-small cell lung cancer(NSCLC);cell proliferation;signaling pathway;expression regulation