利用大花咸豐草化合物polyacetylenic glucoside抑制血管生成之功能研發血管生成之實驗動物平台

外文標題: 
The anti-angiogenic effect of a polyacetylenic glucoside from Bidens pilosa and an angiogenesis animal model establishment
校院系所: 
中興大學獸醫學系暨研究所
指導教授: 
張力天
出版年份: 
2012年
主題類別: 
摘要: 

癌症為全球高罹患率與高致死率的疾病,而腫瘤的缺氧導致血管生成在腫瘤生長與轉移扮演著重要角色,故專一性抑制腫瘤血管的生成為治療腫瘤與預防轉移的方法之一。目前研究指出,大花咸豐草具有改善糖尿病、增加免疫力、抑制血管生成及抗癌等功能。本論文研究的cytopiloyne(CP),為一種萃取自大花咸豐草的polyacetylenic glucoside。由缺氧環境的in vivo及in vitro實驗數據指出,CP具有抑制腫瘤在Matrigel引致的血管生成及減少腫瘤細胞在缺氧環境下之存活率;protein kinase Cα(PKCα)在缺氧的腫瘤細胞中會增加其表現,導致腫瘤的增生與轉移,而CP可以有效減少PKCα蛋白的表現,故CP可能會透過抑制PKCα來減少腫瘤的血管生成。除此之外,藉由CAM、血管內皮細胞之微管生成與Matrigel plug實驗得知,CP也可以直接作用於血管內皮細胞來抑制血管生成。因此,推測CP具有抑制血管生成之能力,並期望可用來治療腫瘤及預防轉移。最後,為探究CP抑制腫瘤血管生成的原因,我們建立cytopiloyne receptor(CPR)基因剔除小鼠,且由Matrigel plug實驗發現CPR基因剔除小鼠不會像對照組wild type小鼠容易生成血管,故印證CPR基因與血管生成之調控有關。綜合以上實驗,由天然物建立轉譯醫學以開發藥物產品是可行的。

外文摘要: 

Cancer is a disease with high incidence and leading cause of death worldwide. Angiogenesis which caused by tumor hypoxia is crucial for tumor growth and metastasis; therefore, anti-angiogenesis therapy is one of the most promising anti-cancer preventable and therapeutic strategies. Bidens pilosa, a traditional herb medicine and edible plant, owned therapeutic bioactivity on various disease, particularly anti-hyperglycemia, anti-bacteria, anti-angiogenesis and anti-cancer effects. In this study, we provide several lines of evidences showing that cytopiloyne (CP), a polyacetylenic glucoside from Bidens pilosa, has anti-angiogenic activities. Firstly, CP inhibited sponge/Matrigel plug angiogenesis from tumor cells in vivo and decreased the survival of tumor cells on hypoxic conditions in vitro. Besides, CP declined PKCα protein expression which leads to the growth and spread of tumors under hypoxia. In conclusion, CP inhibited tumor angiogenesis through PKCα. Secondly, inhibitory effects of CP on endothelial angiogenesis in vivo and in vitro by chick chorioallantoic membrane (CAM) assay, tube formation of SVEC4-10 cells and Matrigel plug assay. Taken together, these results suggest that CP acts as an angiogenesis inhibitor and might be useful for preventing and treating hypervascularized cancers. Finally, we established cytopiloyne receptor (CPR) knockout mice which reduced the effect of angiogenesis through Matrigel plug assay. To sum up, it might avail to develop new medicine by investigating the molecular mechanism of CPR gene.