新型化合物W-1-32靶向XIAP蛋白调控食管鳞癌侵袭转移的作用及机制研究

我国是世界上食管癌患者最多的国家且病理类型多为食管鳞状细胞癌（ESCC），其预后较差的主要原因是肿瘤侵袭性强且早期易发生转移，目前一线治疗药物匮乏。寻求ESCC新的治疗靶点和靶向药物具有重要的现实意义。课题组前期研究发现XIAP在ESCC临床样本高表达与肿瘤淋巴结转移相关且提示不良预后，XIAP可能在ESCC侵袭转移过程中发挥重要作用。课题组通过虚拟对接和空间分析发现新型化合物W-1-32与XIAP具有非常好的结合活性，W-1-32处理后XIAP蛋白表达降低且ESCC细胞迁移能力明显下降。本课题拟在前期基础上，对W-1-32的作用效果进行体内外活性验证，结合表面等离子体共振和微量热泳动等技术研究W-1-32与XIAP的相互作用，进而探索W-1-32与XIAP结合的关键结构域，明确具体作用机制。新型化合物W-1-32有望成为抗ESCC的新药先导化合物，本项目的顺利实施将为其开发利用奠定基础。

China has the largest number of patients with esophageal cancer in the world, and the most pathological type is esophageal squamous cell carcinoma (ESCC). The main reasons for the poor prognosis of esophageal squamous cell carcinoma (ESCC) are the aggressive nature of the tumor and the tendency of early metastasis. At present, there is a lack of first-line treatment drugs for ESCC. It is of great practical significance to seek new therapeutic targets and targeted drugs for ESCC. Previous studies found that the high expression of XIAP in clinical samples of ESCC was associated with tumor lymph node metastasis and suggested poor prognosis. XIAP may play an important role in the invasion and metastasis of ESCC. Through virtual docking and spatial analysis, we found that the novel compound W-1-32 had a very good binding activity with XIAP, and the expression of XIAP protein and migration ability of ESCC cells were significantly decreased after treatment with W-1-32. On the basis of previous studies, this study intends to verify the action effect of W-1-32 in vivo and in vitro, and study the interaction between W-1-32 and XIAP by combining surface plasmonic resonance and micro-thermokinesis techniques, so as to explore the key structural domains of W-1-32 and XIAP, and clarify the specific mechanism. The new compound W-1-32 is expected to be a new lead compound against ESCC, and the smooth implementation of this project will lay a foundation for its development and utilization.