H1和H3型受体介导组胺双向调控肝癌细胞增殖的作用机制研究

项目名称： H1和H3型受体介导组胺双向调控肝癌细胞增殖的作用机制研究

项目编号： No.81472298

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： 胡静

作者单位： 中国人民解放军第四军医大学

项目金额： 70万元

中文摘要： 组胺（HA）作为一种重要的自体活性物质，在肿瘤研究中日益受到重视。以往文献报道，HA可激活四种不同类型HA受体（H1、H2、H3、H4）发挥正向或负向调控作用。我们在肺癌中的研究发现，HA可通过激活H4型受体抑制肺癌细胞增殖，然而HA及其受体在肝癌进展中发挥何种作用及其机制尚不明确。我们前期预实验结果表明，HA受体呈现明显的肝癌特异性表达模式，H1和H3型受体异质性高表达；初步细胞学实验表明激活H1或H3型受体，可显著促进或抑制肝癌细胞增殖，但其具体作用机制亟待阐明。基于上述发现，本项目拟在明确组胺H1和H3型受体表达与肝癌临床病理特征及预后相关性的基础上，借助组织标本、细胞和荷瘤小鼠模型，利用特异性激动剂和拮抗剂、过表达及RNA干涉、Ca2+荧光定量、蛋白抗体芯片等技术，系统分析H1和H3型受体在HA调节肝癌细胞增殖中的双向作用及分子机制，为肝癌防治提供新的理论支持和潜在分子靶点。

中文关键词： C09_肝和肝内胆管肿瘤；组胺；H1型受体；H3型受体；增殖

英文摘要： Histamine (HA), a crucial autacoid in human, has been gaining remarkably importance for current tumor researches in these years. Previous reports indicate that HA generates its positive and negative regulation through binding to its four receptors (H1, H2, H3, H4). Our preliminary study suggests HA could activate H4 receptor and thus inhibits proliferation of pulmonary cancer cells. However, the effect and potential mechanism of HA and its receptors in hepatocellular carcinoma (HCC) remains to be investigated. Another pilot studies reveals that H1 and H3 are expressed in both HCC patient samples and HCC cell lines. Following study indicated the activation of H1 or H3 receptors in such cells could promote or inhibit their proliferation, respectively. But its underlying mechanisms needs further research. Based on these novel findings, our goal in this project is to characterize the relation between H1 and H3 expression and the pathological features or clinical prognosis in HCC. Taking advantage of histological examine on patient tissue samples, cells and tumor-planted mice model, and by using methods such as treatment of agonist and antagonist of HA receptors, overexpression and knockdown of their mRNA expressions, Quantification of cellular calcium, and protein chip, we could systematically analyze the distinctive roles of H1 and H3 in regulation of HCC cells. And thus provide novel insights and putative therapeutic target for treatment of such patients.

英文关键词： Hepatocellular Carcinoma;Histamine;Histamine Receptor H1;Histamine Receptor H3;Prolliferation