中文摘要
血管生成是肿瘤生长、转移等的关键环节,它是HIF-1α启动的血管生成信号级联反应的结果;TGF-β1通过MAPK信号通路调控HIF-1α,影响血管生成。故干预TGF-β1/MAPK/HIF-1α调控体系的关键靶点已成为临床抗肿瘤研究新热点。黄芪-莪术是临床常用配伍。前期研究发现,经验方扶正散结方中益气扶正和活血化瘀两组中药抗肿瘤血管生成作用较突出,且与HIF-1α通路有关,联合应用时效果会得到增强,分析黄芪-莪术配伍是合用后效果加强的主要原因。为证实并阐明其机制及可能的物质基础,本项目拟利用动物及细胞实验,分别取黄芪、莪术及其已知相关活性成份黄芪总皂苷、黄芪多糖和姜黄素、β-榄香烯,从TGF-β1/MAPK/HIF-1α通路入手,运用免疫组化、蛋白印迹、RT-PCR等生物学技术,观察单独及联合应用时对该通路的影响,以阐明其配伍应用时抗肺癌血管生成作用机制及可能的物质基础,为临床提供依据。
英文摘要
Angiogenesis plays an important role in malignant tumor cell proliferation, metastasis, it is the result of the cascade reaction of angiogenesis start by HIF-1α.Through the MAPK signaling pathway, TGF-β1 regulate the HIF-1α expression, and intervene the process of tumor angiogenesis,intervention of the key targets in TGF-β1/MAPK/HIF-1α signaling pathway is a new research hotspot to inhibit tumor angiogenesis. The compatibility of Astragalus-zedoariae is an experienced prescription and our previous study found that the YiQiFuZheng and HuoXueHuaYu in the Fuzheng Sanjie prescription can interfere the HIF-1α expression and effect the tumor angiogenesis, the combined application can enhance the effects, the main reason for improving curative effective is the combination of Astragalus-zedoary. In our project, the alone and combined application of Astragalus, Zedoariae and Radix Astragali Total Saponin, Astragalus Polysaccharide, curcumin, β-elemene be used to do the in vivo and in vitro experiments. By immunohistochemistry, Western Blotting and real-time PCR technique to observe the key factors expression in TGF-β1/MAPK/HIF-1α signaling pathway, to expound the Astragalus-zedoariae molecular mechanism of Anti-angiogenic on lung carcinoma, to provide the basis for clinical application.
