半枝莲活性成分双向调节VEGF与DC机制新探索

项目名称： 半枝莲活性成分双向调节VEGF与DC机制新探索

项目编号： No.30873343

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 卜平

作者单位： 扬州大学

项目金额： 28万元

中文摘要： 本项目以VEGF/DC为靶点，从整体动物、组织、细胞、CML、临床等五个层面探索半枝莲活性成分抑制血管生成和增强肿瘤免疫功能的双向调节作用，结果表明：⑴#32963;癌患者血清、组织中均存在VEGF升高DC下降的恶性循环链。⑵#21322;枝莲黄酮类、多糖类化合物在体外均具有抑制肿瘤细胞和内皮细胞增殖、诱导肿瘤细胞凋亡、抑制uPA及p-Stat3蛋白表达的作用，其作用机理可能是通过抑制Jak/Stat3信号途径从而抑制uPA蛋白的表达，或直接抑制uPA蛋白的表达；半枝莲黄酮类化合物在体外具有抑制肿瘤细胞Survivin蛋白表达、促进PTEN蛋白表达的作用，其作用机理可能是通过下调Survivin，上调PTEN，抑制Survivin对VEGF的正调控，增强PTEN对VEGF的负调控，借以达到下调VEGF的表达⑶CML细胞试验结果表明：半枝莲黄酮类化合物阻滞SGC-7901细胞于S期，阻止细胞从S期至G2期转移。 本研究证实了半枝莲黄酮类、多糖类化合物均具有下调VEGF抑制血管生成和增强DC肿瘤免疫功能的双向调节作用，为中药有效活性成分治疗恶性肿瘤开辟一条新的道路，2项国家授权发明专利正在转让中。

中文关键词： 半枝莲活性成分 ；VEGF；DC；

英文摘要： The project aimed to investigate effects of active components in scutellaria barbata on bi-directional regulating of anti-angiogenesis and immune function targeted to VEGF/DCs from five levels of laboratory animal, tissue, cell, CML, and clinic in tumor. Results showed 1) there were vicious circle chains of increased VEGF level while decreased DCs both in peripheral blood and in cancerous tissues of gastric cancer patients. 2) Flavonoids and polysaccharides extracted from scutellaria barbata inhibited proliferation of tumor cells and endothelial cells, and induced apoptosis of tumor cells in vitro. Expression of uPA and p-STAT3 were down-regulated with treatments of these compounds, either as an indirect result of JAK/STAT3 signaling inhibition, or uPA expression was inhibited by compounds directly. In addition, flavonoids of scutellaria barbata could inhibit survivin expression whereas enhance expression of PTEN in tumor cells in vitro. We inferred that decreased survivin level inhibited positive regulation of VEGF by survivin, and increased PTEN level promoted negative regulation of VEGF by PTEN. As a result, VEGF production of tumor cells was down-regulated. 3) CML tests displayed that flavonoids of scutellaria barbata arrested the cell cycle of SGC-7901 cells at S phase by preventing cycle transferring from S phase to G2 phase. This study demonstrated that flavonoids and polysaccharides of scutellaria barbata had bi-directional regulating effects against tumor, which was manifested by inhibition of angiogenesis via down-regulating of VEGF and promotion of immune functions via enhancing DC functions. It will create a new way in the therapy of cancer with active components of Chinese medicine. Two government authorized patents are being transferred to companies.

英文关键词： Active components of scutellaria barbata; VEGF; DC