白细胞介素-33促进结直肠肿瘤干细胞活性机制研究

项目名称： 白细胞介素-33促进结直肠肿瘤干细胞活性机制研究

项目编号： No.81502572

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李永奎

作者单位： 华中科技大学

项目金额： 18万元

中文摘要： 肿瘤干细胞的自我更新能力，被认为是肿瘤恶性转化和产生耐药性的根本原因，而肿瘤微环境的慢性炎症环境对维持肿瘤干细胞活性至关重要。我们和其他研究证实，炎症因子白细胞介素-33（IL-33）与结直肠肿瘤进程密切相关，但具体调控机制尚不清楚。在前期研究中，我们首次发现结直肠肿瘤细胞可作为IL-33直接作用的靶细胞，IL-33能促进原代结直肠肿瘤细胞在裸鼠皮下的致瘤能力、在体外的成球能力和对化疗药物的耐药性。且基因表达筛选结果显示，IL-33能提高干细胞核心基因OCT3/4、NANOG在结直肠肿瘤细胞中的表达水平。. 因此，我们提出IL-33作为肿瘤微环境的重要调控因子，能促进结直肠肿瘤干细胞活性，而诱导恶性转化和产生耐药性。本项目致力于阐明IL-33调控结直肠肿瘤干细胞活性的机制，为从源头上抑制肿瘤的恶性转化和耐药性提供有效的治疗靶位。

中文关键词： C08_结；直肠肿瘤；白细胞介素-33；干细胞活性；信号通路；炎症因子

英文摘要： The self-renewal of tumor stem cells is considered as the prime cause of tumor malignant transformation and resistance to chemotherapeutics. The chronic inflammation in tumor microenvironment is essential for sustaining the stemness of tumor cells. We and other researchers have verified that the inflammatory factor IL-33 is closely interrelated with colorectal tumor，but the regulatory mechanism remains unclear. In previous study, we have firstly discovered that colorectal tumor cells can be the direct target of this cytokine, and that IL-33 can promotes the tumorigenesis of primary colorectal tumor cells in nude mice, the capability of sphere formation and the resistance to chemotherapeutics. The expression array of genes reveals that IL-33 increase the expression of the stem cell core genes OCT3/4 and NANOG in colorectal tumor cells. . Thus，we raise the hypothesis that IL-33, as an important regulatory factor in tumor microenvironment, enhances the stemness of colorectal tumor cells, consequently inducing tumor malignant transformation and drug resistance. This project focuses on clarifying the mechanisms that IL-33 regulates the stemness of colorectal tumor cells, which may provide a new effective target to prevent tumor malignant transformation and drug resistance.

英文关键词： colorectal tumor;interleukin-33;stemness;signal pathway;inflammatory factor