TLR4途径信号转导通路介导黄芪多糖对乳腺癌的免疫调节机制研究

项目名称： TLR4途径信号转导通路介导黄芪多糖对乳腺癌的免疫调节机制研究

项目编号： No.81473388

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： 鲍依稀

作者单位： 重庆医科大学

项目金额： 71万元

中文摘要： 临床上中药被广泛用于肿瘤患者的辅助放化疗，促进机体免疫机能的恢复，但大多数中药调节免疫的机制尚不清楚，因而在西方国家的应用受到限制。现研究表明黄芪多糖（APS）具有免疫调节抗肿瘤作用，预实验初步显示， APS可使TLR4通路中TLR4、MyD88、TRIF等基因和蛋白水平明显升高，但APS是通过TLR4的MyD88依赖还是非依赖途径，或是两条途径同时发挥作用尚不清楚。因此我们拟采用体外巨噬细胞和体内乳腺癌动物模型进行验证，首先建立EAC实体型荷瘤小鼠（自发性乳腺癌）巨噬细胞培养模型与EAC实体型荷瘤小鼠模型，应用定量PCR 、蛋白免疫印迹和阻断剂等先进实验技术，对APS免疫调控TLR4信号通路进行研究，然后采用基因缺陷EAC实体型荷瘤小鼠加以验证，此类研究目前国内外文献未见报道，为全面揭示APS免疫调节抗肿瘤机制、结构修饰及靶向治疗，以及免疫类抗肿瘤中药方剂的研制提供理论依据及技术平台。

中文关键词： 黄芪多糖；免疫调节；TLR4信号通路

英文摘要： Traditional Chinese Medicine (TCM) is widely used in radiotherapy and chemotherapy in cancer patients,it can promote recovery of immune function, but the majority of TCM immune mechanism is unclear and therefore has limited application in the western world. At present research shows that Astragalus polysaccharide (APS) has antitumor activity of immune regulation, preliminary experiments show that the levels of genes and proteins such as TLR4 , MyD88 and TRIF of TLR4 pathway were markedly elevated by APS, but APS mediated through MyD88-dependent or non-dependent way of TLR4 pathway or two pathways at the same time play a role is not yet clear. So we use macrophages in vitro and the mice models of breast cancer in vivo for validation. Firstly, EAC tumor-bearing mice (spontaneous breast cancer) macrophagocyte training model and EAC tumor-bearing mice model was established, and then applicate quantitative PCR, western blot ,blocking agent and so on. In order to investigate APS immune regulation TLR4 signal pathway, we used genetic defects EAC tumor-bearing mice for verification, such studies have not been reported at home and abroad,the results will reveal the immunomodulatory anti-tumor mechanisms , structural modifications and targeted therapy of APS, and also provide the theory basis and technology platform for the development of TCM formula .

英文关键词： astragalus polysaccharide;immunonmodulatory;TLR4 signal pathway