IL-17F在结肠癌血管生成中的作用及其机制研究

Colorectal cancer incidence rates increase rapidly. Development of efficient prevention programs is imminent. Anti-tumor angiogenesis is an important strategy for the treatment of colorectal cancer. Interleukin-17F (IL-17F) could mediate inflammatory response and also inhibit the tube formation of endothelial cells in vitro. Our previous study was the first to show that IL-17F could inhibit the growth of colorectal tumor. Based on the preliminary work, we first put forward the hypothesis "IL-17F could affect tumor angiogenesis through direct inhibition of the tube formation of tumor endothelial cells, regulation of tumor cells secreting VEGF and recruitment of immune cells to the tumor microenvironment". In this project, we plan to construct colon cancer cells CT26 with over-expression or down-regulation of IL-17F. In vitro, we will check the growth, migration and tube formation of endothelial cells treated by conditioned medium from the cancer cells. In vivo, we will check the the number, proliferation and apoptosis of endothelial cells in the transplanted tumor of BALB/c mice. We will further analysis the molecular signaling pathways of IL-17F regulated VEGF secretion from the cancer cells, and the recruitment of pro-angiogenesis N2 neutrophils and M2 macrophages in the transplanted tumor microenvironment. This study will help to elucidate the mechanism and regulation of colon cancer angiogenesis, and provide new intervention targets for the treatment of colon cancer.

结直肠癌发病率不断攀升，研发高效的防治方案迫在眉睫。抗肿瘤血管生成是治疗结直肠癌的重要策略。白细胞介素-17F (IL-17F) 除了参与炎症反应还可以抑制内皮细胞体外管腔的形成。我们的前期研究首次报道IL-17F可以抑制结直肠癌的生长。在前期工作的基础上，我们率先提出假说"IL-17F通过直接抑制肿瘤血管内皮细胞的管腔形成、调控肿瘤细胞分泌VEGF和招募免疫细胞至肿瘤微环境三个方面影响肿瘤血管的生成"。本项目拟建立IL-17F表达水平不同的小鼠结肠癌CT26细胞株。体外观察肿瘤细胞条件培养基对血管内皮细胞生长迁移和管腔形成的影响；体内分析肿瘤细胞BALB/c小鼠移植瘤中血管内皮细胞的数量和生长特性。进一步检测IL-17F影响肿瘤细胞分泌VEGF的分子通路，及招募促血管生成亚型的中性粒细胞N2和巨噬细胞M2浸润移植瘤的情况，阐释IL-17F影响肿瘤血管生成的机制，为结肠癌的治疗提供新靶点。