果胶抑制半乳凝素-3介导的肿瘤血管生成机制研究

果胶结构复杂，活性多样，是药用植物的有效成分。果胶能抑制半乳凝素-3（Gal-3）介导的肿瘤血管生成，但作用机制尚不清楚。本项目用不同结构的柠檬和人参系列果胶，沿着"果胶-Gal-3-配体-细胞"的路线，借助体内外血管生成模型和现代生物学技术，逐步深入地研究果胶抑制Gal-3介导的肿瘤血管生成的作用机制。研究内容包括：1）果胶作用于内源（血管内皮细胞自身表达）还是外源（来自于肿瘤组织）的Gal-3；2）与哪些Gal-3配体有关，即功能配体是什么；3）果胶对功能配体在细胞膜上表达和分布的调节机制。项目的特色与创新之处在于采用层层深入多方位研究的策略，首次研究果胶抑制Gal-3介导的血管生成机制，充分考虑了内源和外源Gal-3的不同作用以及配体的动态变化，预计会得到较好的成果。研究结果对促进果胶作为Gal-3抑制剂的研究以及糖生物学的发展会有积极的作用.

Pectin is a type of acidic polysaccharides with complex structures. It is an active component of medicinal plants and possesses various biological activities. Pectin has been shown to inhibit galectin-3 (Gal-3)-mediated tumor angiogenesis, but the underlying mechanism is not elucidated. In this project, we will investigate the mechanism of pectin inhibition of tumor angiogenensis using a series of modified citrus and ginseng pectins. We shall follow the path of 'pectin - Gal-3 - ligands - cell' and use in vitro and in vivo angiogenesis models together with some modern techniques to study 1) which population of Gal-3 is the target of pectin, the exogenous Gal-3 (produced by tumor tissues) or endogenous Gal-3 (produced by vascular endothelial cells); 2) what Gal-3 ligands are involved in pectin inhibition, in other words, what are the functional Gal-3 ligands; 3) the modulation effect and mechanism of pectin on Gal-3 ligands. This is the first detailed mechanism investigation of pectin inhibition of Gal-3-mediated angiogenesis. The distinct feature of this proposal is using different pectins and Gal-3 proteins to probe the inside of pectin action, and focusing on not only the inhibition of pectin to Gal-3, but also the down-stream effectors of Gal-3, i.e. the ligands of Gal-3. In addition, this proposal takes the difference between endogenous and exogenous Gal-3 and the homeostasis of Gal-3 ligands into account. Thus, it shall provide novel and accurate results which will be valuable to the development of potent and nontoxic Gal-3 inhibitors.