HMGB1影响上皮间质转化在原发性肝细胞癌侵袭、转移中的作用及其机制研究

项目名称： HMGB1影响上皮间质转化在原发性肝细胞癌侵袭、转移中的作用及其机制研究

项目编号： No.81201619

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 周蓉蓉

作者单位： 中南大学

项目金额： 23万元

中文摘要： 高迁移率族蛋白1（HMGB1）是一种肿瘤相关炎症因子。前期工作发现：HMGB1可以促进肝癌细胞增殖，沉默HMGB1 基因可以明显减弱肝癌细胞的侵袭、迁移能力，提示HMGB1与原发性肝细胞癌（HCC）侵袭、转移的密切相关性。上皮间质转化（EMT）因能使肿瘤细胞获得侵袭、迁移能力，而在HCC的转移中起非常重要的作用。基于此，本课题拟应用RNA干扰和质粒转染等技术，研究HMGB1表达水平的改变对肝癌细胞EMT的影响；进一步，利用报告基因系统，揭示HMGB1对EMT通路的分子调节机制；选用免疫缺陷型SCID小鼠原位移植瘤模型，观察HMGB1对HepG2细胞移植瘤EMT过程及生长、转移的影响。本研究有望阐明HMGB1对肝癌细胞EMT的作用及其相关分子机制，为以HMGB1为靶点的预防和阻断HCC转移的治疗提供依据。

中文关键词： 高迁移率族蛋白1；原发性肝细胞癌；上皮间质转化；核转录因子kappa B；转移

英文摘要： High-mobility group box 1 (HMGB1) is a kind of cancer related inflammatory mediator. Our previous work found that, HMGB1 promoted proliferation of hepatocellular carcinoma (HCC) cells and downregulation of HMGB1 obviously inhibited the migration and invasive ability of these cells. These results suggested that HMGB1 is closely associated with migration and invasion of HCC. Epithelial to mesenchymal transition (EMT) plays important roles in the metastasis of HCC, for it make cancer cells more motile, migratory and invasive. In this study, plasmid transfection and RNAi techniques will be used to investigate effects of HMGB1 alteration to the EMT process of HCC. Further more, report gene system will also be used to reveal the molecular regulatory mechanism of HMGB1 to the process of EMT. Orthotopic transplantation tumor model with immunodeficiency SCID mouse will also be invited to observe influence of HMGB1 to the process of EMT, tumor growth and metastasis of the transplanted HepG2 cells. This study will clarify the role of HMGB1 and its related pathways in the EMT process of HCC and provide evidence for therapeutic interventions targeted HMGB1 in the prevention and interruption of HCC metastasis.

英文关键词： high-mobility group box 1；hepatocellular carcinoma；epithelial to mesenchymal transition；nuclear transcription factor kappa B；metastasis