黄芪皂苷调控CD45蛋白酪氨酸磷酸酯酶介导抗肿瘤免疫分子机制的研究

项目名称： 黄芪皂苷调控CD45蛋白酪氨酸磷酸酯酶介导抗肿瘤免疫分子机制的研究

项目编号： No.81460624

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 万春平

作者单位： 云南中医药大学

项目金额： 50万元

中文摘要： 机体的免疫功能低下与肿瘤的发生发展密切相关，因此，通过药物增强机体免疫功能，更好地发挥机体抗肿瘤免疫监杀机制，已成为肿瘤治疗的重要手段。课题申请人前期通过CD45高通量筛选模型首次发现黄芪皂苷能够显著激活CD45蛋白酪氨酸磷酸酯酶（PTPase），从而增强细胞免疫功能。基于黄芪皂苷体内抗肿瘤疗效已明确，我们认为黄芪皂苷可能通过调控CD45 PTPase介导抗肿瘤免疫作用，本项目拟在CD45PTPase酶动力学模型上，进一步分析黄芪皂苷对其激活作用的特异性；构建CD45（+）和 CD45（-）Jurkat T细胞模型、CD4+ T细胞活化模型、FVB/neu转基因自发乳腺癌荷瘤小鼠模型，从增殖、细胞因子分泌、CD45信号传导通路关键信号蛋白的磷酸化状态及转录因子表达等多个层面，揭示黄芪皂苷调控CD45信号转导通路介导抗肿瘤免疫的新机制，为黄芪抗肿瘤免疫疗法、传承与创新和新药研究奠定理论基础。

中文关键词： 黄芪皂苷；CD45蛋白酪氨酸磷酸酯酶；抗肿瘤免疫；T细胞抗原受体；转录因子

英文摘要： Compromised immune system is tightly linked with initiation and progression of tumor.Conversely, it is an important strategy to control tumor progression by enhancing immune function.Through high-throughput screening model of CD45 PTPase, our previous study firstly reported that astragaloside could significantly activate CD45 PTPase, thus to enhance cellular immunity. Considering the well-established in vivo anti-tumor effects of astragaloside, we then hyperthesize that the astragaloside induced anti-tumor immunological effect through regulating CD45 PTPase. This proposed study will also further investigate the mechanism of astragaloside to activate CD45 PTPase. To further investigate the changes of upstream and downstream in CD45-mediated signaling pathway of CD4+T cell after intervention with astragaloside, CD45-positive Jurkat T cell line (JE6.1)and CD45-negative Jurkat T cell Line, TCR cross-linking-induced CD4+ T cell activation and FVB/neu transgenic spontaneous breast cancer mice model will be used. The immune reaction will be monitors from the aspects of proliferation, cytokine production, phosphorylated signal molecules and expression of transcription factor. Collectively, the proposed study will explore the new anti-tumor mechanism of astragaloside and enhance the theoretical foundation for antitumor immunotherapy of Astragalus, inheritance and innovation and new drugs research.

英文关键词： Astragaloside;CD45 protein tyrosine phosphatase;Antitumor immunity;T cell antigen receptor;Transcription factor