CIAPIN1,一个调控肿瘤血管生成的新分子的功能研究

Previously, we reported a new apoptosis-related gene CIAPIN1, and we found that it could regulate tumoregenesis, tumor cell cycle arrest and tumor multidrug resistance. Upregulation of CIAPIN1 could significantly inhibit gastric cancer cells and vascular endothelial cells proliferation and mediate the expression level of angiogenic molecule VEGF and CDC42. Therefore we think that CIAPIN1 may play an important role in tumor angiogenesis. In this research, we want to use the gene transfer technology to change CIAPIN1 expression and function in gastric cancer cells and vascular endothelial cells, using in vitro and in vivo experiments to observe whether CIAPIN1 could affect cells angiogenesis, using human angiogenesis gene chips to explore CIAPIN1 involved tumor angiogenesis signal pathways, and further using tandem affinity purification technology, time-of-flight mass spectrometry, yeast two-hybrid, co-immunoprecipitation to explore CIAPIN1's binding molecule. If we could prove that CIAPIN1 is a novel tumor angiogenesis regulatory molecule, it could lay solid foundation for us to better understanding the tumor angiogenesis process, and to explore new gene therapy methods.

我们是国际上率先对凋亡相关基因CIAPIN1的功能进行报道的单位,发现CIAPIN1可调控肿瘤发生，细胞周期阻滞和肿瘤的多药耐药；上调CIAPIN1能显著抑制胃癌细胞和血管内皮细胞的生长，且能调控血管生成相关分子VEGF，CDC42的表达。因此认为CIAPIN1在肿瘤血管生成中起重要作用。本研究拟利用基因转染技术改变CIAPIN1在胃癌细胞和血管内皮细胞中的表达和功能，借助体内外实验研究CIAPIN1对细胞诱生血管能力的影响，通过人血管生成基因芯片探索CIAPIN1参与肿瘤血管生成的调控途径，并利用串联亲和纯化、飞行时间质谱、酵母双杂交、免疫共沉淀等技术探讨CIAPIN1发挥血管调控作用时可能结合的相关分子。若能证明CIAPIN1是一个新的肿瘤血管生成调控分子，可为深入理解肿瘤血管生成的分子事件，探讨新的基因治疗方法奠定基础。