缺氧诱导血管生成是肝癌的重要生物学特征。HIF-1α/VEGF信号通路在缺氧下激活并与肝癌的预后关系密切。我们前期发现，天冬多糖制成胶剂在大鼠肝动脉栓塞治疗肝癌具有较好的疗效，且毒性低。进一步研究发现缺氧下天冬多糖处理的肝癌细胞HIF-1α、VEGF表达明显下调，但具体机制不详。我们推测，天冬胶介入治疗肝癌可能是直接调控HIF-1α或影响其上、下游基因，来调控HIF-1α/VEGF信号通路，从而抑制肿瘤血管生成及侵袭转移。本项目拟制备HIF-1α基因过表达和敲除的人肝癌细胞模型以及裸小鼠移植瘤模型，运用过表达、RNA干扰、免疫沉淀等技术手段，基于HIF-1α/VEGF信号通路系统研究天冬多糖抑制肿瘤血管生成、增殖、侵袭和转移。从基因、蛋白质和功能诸方面揭示天冬胶介入栓塞治疗肝癌的机制，阐明其抗血管生成的信号通路，为提高中药TACE治疗肝癌的临床疗效提供实验依据。

Angiogenes induced by hypoxia is one of predomiant phenotypes of primary liver cancer ,features that could be important in the development of new interventional embolization drugs. HIF-1α/ VEGF signaling pathway is activated in hypoxia and related to features of malignancies. Recently, we found that asparagus colloid made from asparagus polysaccharides is a good performance of embolic agents. It can bring anti-cancer efficacy after treatment of liver cancer by hepatic artery embolization, and show little toxicity to the host. Interestingly, our preliminary data indicate that refined asparagus colloide can significantly low HIF-1α、VEGF’s expression to a certain extent. We hypothesize that HIF-1α may be the key of molecular-targeted of asparagus polysaccharides.This project is designed to investigate the functions of HIF-1α/ VEGF signaling pathway in live tumor progression, combined with gene transfection, RNA interference, RT-PCR, immunoprecipitation.We will determine the contribution of Asparagus polysaccharides to tumor cell proliferation,survival,migration and invasion due to hypoxia. We will also investigate the underlying molecular mechanisms,mainly focused on HIF-1α/ VEGF signaling pathway.Then we will study the biological roles of HIF-1α/ VEGF signaling pathway in live tumor proliferation, invasion and metastasis using a xenograft animal model. Thus, this proposed study will characterize the novel roles and pathways of HIF-1α/ VEGF signaling pathway in live cancer progression. The information gained should be of help in developing new therapeutic approaches to treat malignant liver tumour.