AAV病毒介导的Mig-6基因转染联合TACE通过调控细胞周期治疗肝细胞癌的分子机制研究

项目名称： AAV病毒介导的Mig-6基因转染联合TACE通过调控细胞周期治疗肝细胞癌的分子机制研究

项目编号： No.81501564

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李紫璇

作者单位： 中国医科大学

项目金额： 18万元

中文摘要： 肝细胞癌患者经肝动脉化疗栓塞（TACE）后残余肿瘤复发是影响患者预后主要问题。前期实验我们发现抑癌基因Mig-6在肝癌中表达显著低于癌旁组织，并对肿瘤细胞周期进程及增殖能力有显著影响。因此本项目我们拟采用TACE联合腺相关病毒（AAV）介导的Mig-6基因转染方法对兔VX2肝癌移植瘤模型进行介入治疗，观察这种新的联合治疗模式疗效同时，对AAV介导的Mig-6基因转染治疗肝癌的分子机制深入研究。试图验证Mig-6做为一个细胞周期特异性表达基因，如何通过抑制MAPK通路的活性抑制细胞周期素CyclinD1表达，从而抑制肿瘤细胞进入增殖期，抑制肿瘤细胞生长。该研究一方面对阐述Mig-6能通过MAPK/Cyclin D1通路抑制细胞增殖有着重要的理论创新意义；另一方面将为TACE术合并基因治疗提供备选药物；同时创新型基因转染研究方法将为诸多抑癌基因从理论研究到临床应用转化提供了新的研究手段和方向

中文关键词： 血管内介入；经肝动脉化疗栓塞；肝细胞癌；腺相关病毒；丝裂原诱导基因6

英文摘要： Residual tumor recurrence after Transcatheter arterial chemoembolization (TACE) operation is the main problem affecting the prognosis of the patients with hepatocellular carcinoma(HCC). Preliminary experiments we found that the tumor suppressor gene Mitogen inducible gene 6 (Mig-6) was much lower in HCC compared to corresponding normal liver tissue. It had significant effects on tumor cell cycle and proliferation ability. So in this project we intend to use the combined TACE and adeno-associated virus (AAV) mediated Mig-6 gene transfection method on rabbit VX2 liver cancer xenograft model. The project studys the molecular mechanism of AAV mediated Mig-6 transfected in HCC, as well as observes the curative effect of this new combined treatment mode. The project will confirm the mechanism that Mig-6 suppresses the expression of CyclinD1 by inhibiting the MAPK pathway activity, inhibits the tumor cells to enter the cell cycle and inhibits the growth of tumor cells. On one aspect, this project describes of Mig-6 inhibting the proliferation of HCC by MAPK/Cyclin D1 pathway. On the other hand, regard of the important anticancer funtion of Mig-6 ,we can develop it as one of the candidate drugs combined with TACE therapy. In the meanwhile in vivo transfection research methods will be discussed to provide a new direction for the study of many tumor suppressor genes, as well as Mig-6, which may help to accelerate the transformation from basic theory to clinical application.

英文关键词： Endovascular intervention;TACE;hepatocellular carcinoma ;AAV;Mig-6