Periostin在肝细胞癌抗血管生成靶向治疗中的作用及分子机制研究

项目名称： Periostin在肝细胞癌抗血管生成靶向治疗中的作用及分子机制研究

项目编号： No.81201906

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2

项目作者： 王伟

作者单位： 安徽医科大学

项目金额： 23万元

中文摘要： Periostin（PN）是新近发现的一种分泌性糖蛋白，与肿瘤血管生成、侵袭转移和预后等密切相关，但分子机制尚不清楚。肝细胞癌（简称肝癌）是典型的多血管性肿瘤，理论上而言，PN可成为肝癌抗血管治疗的新靶点之一。但迄今国内外针对PN在肝癌中的研究较少。我们近期研究发现，PN与肝癌侵袭转移及肿瘤血管生成相关。因此，本项目拟在前期研究基础上，通过：建立PN过表达或低表达稳转的肝癌细胞系与肝癌裸鼠移植瘤模型，研究PN在肿瘤生长、侵袭、转移以及血管生成中的作用；建立诱导性SD大鼠肝癌模型，探讨特异性阻断PN的活性对血管抑制剂抗癌效应的影响；体外进一步研究PN对肝癌细胞增殖、侵袭等生物学行为的调控作用，并探讨其可能的分子机制。从体内和体外两个层面探索PN在肝癌发生发展、抗血管靶向治疗中的作用及其相关的分子机制，为抗血管生成治疗肝癌提供新靶点。

中文关键词： 肝细胞癌；骨膜蛋白；血管生成；靶向治疗；生物信息学分析

英文摘要： Periostin (PN) is a recently discovered secreted glycoprotein, which is closely related to tumor angiogenesis, invasion, metastasis and prognosis, but the underlying molecular mechanism is still unclear. Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. Theoretically, periostin may become one of the new targets for the anti-angiogenic therapy of HCC. However, so far, there has been less detailed report between periostin and HCC at home and abroad. Recently, we have found that periostin is related with invasion, metastasis and angiogenesis of HCC. Therefore, based on the previous studies, in this project, we aim to: establish hepatoma cell lines with over- or low- expression of periostin under stable transfection and HCC xenografts in nude mice, and use the model to study the biological functions of periostin in HCC tumor growth, metastasis, and angiogenesis; establish a primary SD rat HCC model induced by the chemical carcinogens and investigate the influence of periostin on the anti-cancer effect of vascular inhibitors after blocking its activity by the specific inhibitors; further study the biological functions of periostin in the regulation of HCC cell proliferation, invasion in vitro, and explore its possible molecular mechanisms. In conclusion, this study will explore the effects of periostin

英文关键词： hepatocellular carcinoma；periostin；angiogenesis；targeted therapy；bioinformatics analysis