抗菌肽Cathelicidin在具核梭杆菌诱发结肠癌发生发展中的作用及其机制研究

结肠癌发病的分子机制至今未明，最新研究发现：具核梭杆菌作为口腔致病菌，异常活跃于结肠癌细胞，并与肿瘤的恶性程度存在一定相关性。申请者最新研究表明，内源性抗菌肽Cathelicidin在结肠癌患者肿瘤组织中表达下降，这提示：当肠道表面Cathelicidin低表达时，具核梭杆菌很可能更容易定植并侵袭肠上皮细胞，促进结肠癌发生。故本项目拟开展：（1）外源性Cathelicidin对具核梭杆菌生长及细菌生物膜形成的抑制作用，证明结肠上皮细胞内源性Cathelicidin对具核梭杆菌粘附与侵袭的防御作用；（2）通过Cathelicidin基因敲除小鼠结肠癌模型，以验证内源性及外源性Cathelicidin在具核梭杆菌诱发结肠肿瘤形成中的可能保护作用及机制。本研究将首次阐明Cathelicidin 在具核梭杆菌诱导结肠癌的发病机制中的作用有重要科学价值。

The underlying mechanisms of colon cancer remain to be established. Recent studies reported overabundance of an opportunistic commensal anaerobe in the oral cavity, Fusobacterium nucleatum (Fn), closely related to the degree of malignancy in colon carcinorma tissues. Cathelicidn, an endogenous antimicrobial peptide, plays an important role in the host defense mechanisms. It is reported that low expression level of endogenous Cathelicidin in colon tumor tissue than that of the heathy control, which indicated that Fusobacterium nucleatum may prone to adhere and invade on the colon epithelial cells, then promote colon tumor formation when lack of cathelicidin. In this proposal, we firstly investigate the antimicrobial and anti-biofilm formation activity of cathelicidin on Fusobacterium nucleatum. Furthermore, the protective effect of endogenous cathelicidin on Fn’s adherence and invadence activity to colon epithelial cells will also be explored. Finally, we shall confimed the role of Cathelicidin on Fusobacterium nucleatum induced colon cancer model by use of cathelicidin knockout and wild-type mice. This project will demonstrate the possible mechanisms of Cathelicidin in Fusobacterium nucleatum promote colon cancer.