吴茱萸碱调控IL-6/STAT-3信号通路抑制炎症相关性结直肠癌的机制研究

肠道慢性炎症促进结直肠癌发生，IL-6/STAT-3信号通路是炎癌转化的关键信号通路。阻断IL-6/STAT-3信号通路可有效阻止肠炎进展为结直肠癌，但化学合成小分子药物最突出问题是选择性差、毒副作用大。申请者在国家自然科学青年基金（81202967）资助下，发现吴茱萸碱是一个新的STAT-3通路天然抑制剂，可抑制肿瘤生长和侵袭转移。同时课题组近期研究结果证实吴茱萸碱可显著减轻葡聚糖硫酸钠（DSS）诱导的溃疡性结直肠炎小鼠的炎症程度，但其可否抑制炎症向结直肠癌恶变目前尚不清楚。本课题拟通过建立多种炎症相关性结直肠癌模型观察吴茱萸碱预防结直肠癌发生发展的效果，并考察吴茱萸碱对肠道炎症微环境中肠上皮细胞和炎症细胞的选择性作用，探讨其抑制IL-6/STAT-3信号通路的分子靶点。本项目的顺利实施将从一个全新的角度阐述吴茱萸碱作为IL-6/STAT-3新的天然调控剂在防癌中的作用。

IL-6/STAT-3 signaling pathway is closely associated with inflammation and cancer, STAT-3 is excessive activation and dysfunction in colitis and colorectal cancer. Most colorectal cancer can be prevented by blocking IL-6/STAT-3 signaling pathway, but the most prominent problem of synthetic chemoprevention agents is the poor selectivity and side effect. With the support by the NSFC (81202967), our group found that evodiamine is a new type, natural STAT-3 inhibitor, can inhibit tumor cell growth, invasion and metastasis. In addition, the latest research results confirm that evodiamine can prevent ulcerative colitis progress to colorectal cancer, but its mechanism is not clear. In this study, colitis-associated colon model is established to evaluate prevention effect of evodiamine, and investigated the effect of evodiamine on intestinal epithelial cells and inflammatory cells in the inflammation microenvironment of intestinal. Explore the mechanism that evodiamine control IL-6/STAT-3 signaling pathways to inhibit occurrence and development of colitis-associated colon.