新基因SARI调控肿瘤血管生成、形态及功能的分子机制研究

肿瘤的生长依赖于血管提供营养和养分，因此，抗血管生成治疗是肿瘤治疗的重要策略。SARI(suppressor of AP-1, regulated by IFN)是近来报导的新基因，它能通过调控AP-1的活性来抑制肿瘤细胞的增殖，诱导肿瘤细胞凋亡，但它是否能调控肿瘤血管生成、血管形态及功能未见文献报导。本课题组前期研究发现，SARI 能显著抑制人脐静脉内皮细胞（HUVECs）成管，抑制小鼠皮下移植瘤生长和肿瘤血管生成，但它如何调控肿瘤血管形态与功能不清楚。基于前期研究结果，本课题将利用HUVECs增值、迁移、成管等实验，结合转GFP基因的斑马鱼模型、小鼠体内血管模型和基因敲除鼠模型以及免疫荧光、Westren blot、免疫组化、基因阻断、电镜等技术，研究SARI调控肿瘤血管生成、血管形态、功能的作用靶点及信号通路，为深入了解SARI基因功能奠定基础，也为设计抗血管生成治疗提供候选靶点。

Nutrition and nutrients provided by blood vessels are necessary for tumor growth, so anti-angiogenesis is an important strategy for tumor treatment. SARI (suppressor of AP-1 regulated by IFN) is a new gene which takes the role of inhibiting tumor cell proliferation and inducing tumor cell apoptosis by regulating AP-1 activity, but whether it can regulate tumor angiogenesis, morphology and function have not been reported. Our preliminary study shows that SARI can significantly inhibit the tube formation of human umbilical vein endothelial cells (HUVECs), inhibit tumor growth and tumor angiogenesis in mice, but the mechanism is unclear. Based on the results we got, HUVECs proliferation assay, tube formation assay and migration assay will be used in the future research. To further study the target and signal pathway of SARI on regulating vessel morphology and function, inhibiting tumor angiogenesis, zebrafish transferred with GFP gene, mice vessel model, gene knockout mice as well as the techniques likeimmunofluorescence, Western blotting,immunohistochemistry,gene interruption, electron microscope will be used in our study. This study will lay a foundation for further understanding the function of SARI, meanwhile it will provide a novel target for anti-angiogenesis gene therapy in clinical research.