项目名称： PPAR β/δ基因在结直肠癌血管生成调控中的作用及分子机理

项目编号： No.81472304

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 杨烈

作者单位： 四川大学

项目金额： 78万元

中文摘要： 近期研究显示，APC/β-catenin/TCF-4信号通路与肿瘤血管生成相关，PPAR β/δ是该信号通路下游基因，在胰腺癌等微环境中参与血管生成开关(angiogenic switch)调控(PNAS 2007;104(31):12890-5)。迄今，结直肠癌微环境中PPAR β/δ对血管生成的作用不清。我们前期研究提示，PPAR β/δ在结直肠癌细胞和血管内皮细胞中均参与VEGF调控并与预后相关，可抑制癌细胞增殖、促进分化(Oncogene、Clin Cancer Res、Dis Colon Rectum、PLoS ONE、J Gastroenter)。据此，我们猜想，PPAR β/δ在结直肠癌中对血管生成的作用如何？是否与调控细胞增殖、分化有关？是否受到APC信号通路的调控？本课题拟采用细胞株实验、斑马鱼及裸鼠移植瘤模型、基质胶栓实验、血管生成蛋白芯片、液相芯片等方法论证上述猜想。

中文关键词： C08_结；直肠肿瘤；PPAR；β/δ；肿瘤血管生成；血管内皮细胞

英文摘要： A recent study shows that, APC/β-catenin/TCF-4 signaling pathway is closely related to tumor-associated angiogenesis and one of its downstream genes,PPAR β/δ,is involed in regulating the angiogenic switch in the microenviorment of pancreatic cancer(PNAS 2007;104(31):12890-5). To date, the role of PPAR β/δ in the angiogenesis of colorectal cancer (CRC) remains unclear.Our preliminary studies show that, PPAR β/δ expressed in cancer cells or in vascular endothelial cells of CRC is involved in modulating the expression of VEGF, and is related the prognosis of colorectal cancer patients,inhibiting the proliferation and faciliating the differentiation of cancer cells (Oncogene,Clin Cancer Res,Dis Colon Rectum,PLoS ONE,J Gastroenterol). Therefore, here we hypothesize that PPAR β/δ may be invovled in regulating the angiogenesis of colorectal cancer,which may be related to its modulation of cell proliferation and differentiation, and may be regulated by APC signaling pathway. In the research proposal, we aim to test this hypothesis by using cell culture experiments,zebrafish model,nude mouse xenograft model,matrigel plug assay,Proteome Profiler Human Angiogenesis Antibody Array and suspension array, etc.

英文关键词： colorectal cancer;PPAR β/δ;tumor-associated angiogenesis;vascular endothelial cell