解整合素-金属蛋白酶ADAM8在肝细胞癌发生发展中的作用机制研究

项目名称： 解整合素-金属蛋白酶ADAM8在肝细胞癌发生发展中的作用机制研究

项目编号： No.81201558

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： 李三强

作者单位： 河南科技大学

项目金额： 23万元

中文摘要： ADAM8是解整合素-金属蛋白酶家族的重要成员，在多种癌症的发生发展过程中起到重要作用，但其与肝细胞癌的关系仍知之甚少。我们的预实验结果表明：ADAM8 分子在肝细胞癌组织和有淋巴结转移的肝细胞癌组织中表达明显升高，在正常肝组织中几乎不表达；重组的ADAM8分子能够促进体外培养的正常肝细胞增殖，抑制肝癌细胞凋亡。ADAM8分子在肝细胞癌的发生发展过程中可能起重要作用，但其作用机制还有待进一步探讨。为此，体内实验我们利用ADAM8基因敲除小鼠和正常小鼠肝癌模型，体外实验利用人肝癌细胞HepG2和正常肝细胞L02，采用免疫组化、蛋白印迹、实时定量RT-PCR、RNA干扰等手段，从分子、细胞、组织以及动物整体水平等多方面探讨ADAM8在肝细胞癌发生发展过程中的重要作用及分子机制。本研究将从ADAM8这个新视点为揭示肝细胞癌发生发展机制奠定基础，有可能为临床肝细胞癌的诊断和治疗提供新的思路。

中文关键词： 肝细胞癌；解整合素-金属蛋白酶8；细胞增殖；细胞凋亡；

英文摘要： ADAM8 is an important member of a disintegrin and metalloprotease (ADAM) family,which plays important roles in many kinds of cancers. But the relationship of ADAM8 with HCC has still been poorly understood. The results of our preliminary experiments showed that the expression of ADAM8 was significantly increased in the tissues of HCC and HCC with lymph node metastasis while it was almost not expressed in normal liver tissues. Recombinant ADAM8 molecule could promote the proliferation of normal liver cells and inhibit the apoptosis of hepatoma cells in vitro experiments. ADAM8 may play important roles in development and progression of HCC. But its mechanism remains to be further explored. Therefore, we will use the liver cancer models of ADAM8 gene knockout mice and normal mice in vivo experiments and use HepG2 of human hepatoma cell and L02 of normal liver cell in vitro experiments. We will adopt immunohistochemistry, Western blot, real-time quantitative RT-PCR, RNA interference and other means to investigate the important roles and molecular mechanism of ADAM8 in development and progression of HCC from the molecule, cell, tissue and whole animal levels.In this study, we will establish foundation for revealing the mechanism of development and progression of HCC from the new viewpoint of ADAM8, which will possibl

英文关键词： HCC；ADAM8；cell proliferation；Cell apoptosis；