基于钠离子通道β亚基的蝎镇痛抗肿瘤缬精甘肽抗肝癌作用机制初探

项目名称： 基于钠离子通道β亚基的蝎镇痛抗肿瘤缬精甘肽抗肝癌作用机制初探

项目编号： No.81202855

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 崔勇

作者单位： 沈阳药科大学

项目金额： 23万元

中文摘要： 肝癌是世界第三大癌症，在中国发病率极高。东亚钳蝎是一种宝贵的来源于药用动物的潜在抗肿瘤药物。目前，关于蝎镇痛抗肿瘤缬精甘肽与肿瘤电压门控钠离子通道β亚基间的作用机制尚不清楚。前期工作已在大肠杆菌表达具有抗肿瘤活性的重组蝎镇痛抗肿瘤缬精甘肽；确定迁移能力不同的肝癌细胞株(Hep 3B，Bel-7402，Hep G2)差异表达特定电压门控钠离子通道β亚基；证明电压门控钠离子通道β亚基与肝癌细胞的迁移相关。本项目针对电压门控钠离子通道β亚基表达存在差异性，分别对三株肝癌细胞进行转染或RNA干扰实验，蝎镇痛抗肿瘤缬精甘肽作用后检测细胞增殖、迁移及侵袭能力变化。研究蝎镇痛抗肿瘤缬精甘肽同肝癌细胞电压门控钠离子通道β亚基作用的相关性，进而寻找药物作用靶点并建立抗肝癌药物筛选模型，从离子通道水平探索蝎镇痛抗肿瘤缬精甘肽的作用机制，开发拥有原创性自主知识产权的中药新品种等方面，奠定必要的物质基础。

中文关键词： 肝癌细胞HepG2；迁移；侵袭；增殖；rAGAP

英文摘要： Hepatocellular Carcinoma (HCC) is the third worst disease in the world with a highly incidence rate in China. The peptide from Buthus martensii Karsch (BmK) is a valuable drug which has the potential antitumor activity. Now it is still dimness that the mechanism between the antitumor-analgesic peptide (AGAP) and the voltage-gated Na+ channel β subunits. Our laboratory has expressed AGAP in E.coli successfully, definited that hepatoma carcinoma cell line with various immigration, such as Hep 3B, Bel-7402, Hep G2, expressed specified β subunits. So we proved that β subunits are connected to the immigration of cells. According to the various expression of β subunits of three strain cells, a series of in vivo experiments including transfection and RNAi were performed. We examined cells multiplication, immigration and invasion after applied AGAP. The purpose of this project is to look for the drug target site and build the screening model of anti-hepatocellular carcinoma drug through researching the relationship between AGAP and the voltage-gated Na+ channel β subunits, explore the mechanism of this peptide in the level of ion channel and develop the variety of Traditional Chinese Medicine with independent intellectual property rights. The research have provided evidence and laid a good foundation for further experim

英文关键词： HepG2；migration；invasion；proliferation；rAGAP