以IRAK1为关键节点探讨CAC发病机制及乌梅丸预防作用

中国人群的结直肠癌发病率和死亡率较高，严重威胁生命健康。慢性炎症是肠道肿瘤的始动因素之一，“炎癌转化”在CAC的发生发展中扮演重要角色，IRAK1及其相关通路可能是CAC发生的关键节点。前期研究发现，乌梅丸可以减少AOM/DSS诱导的小鼠结肠肿瘤的发生，下调IRAK1、MAPK1、p65基因，下调IRAK1、Myd88、p65蛋白的表达，提示IRAK1及其相关通路可能是乌梅丸预防CAC的潜在机制。本研究拟通过乌梅丸干预IRAK1敲除小鼠、IRAK1基因敲减和过表达的HCT116、Lovo细胞系等动物和细胞实验，运用ELISA、免疫荧光、qPCR、Western Blot等技术，观察IRAK1对CAC生成的影响和乌梅丸对IRAK1及IL-1R/IRAK1/NF-κB/MAPK通路的影响，阐明IRAK1在CAC发生的关键作用，诠释乌梅丸预防CAC的潜在作用机制。

In China, Colorectal cancer (CRC) has a high incidence and mortality, which seriously threatens life and health. Chronic inflammation is one of the initiating factors of intestinal cancer. "Inflammatory transformation" plays an important role in the development of colitis-associated colorectal cancer (CAC). Interleukin-1 receptor-related kinase 1 (IRAK1) and its related pathway may be the key node of CAC. Our previous study found that Wumei Pill can reduce the occurrence of AOM/DSS-induced colon tumor in mice, down regulate IRAK1, MAPK1, p65 genes as well as the protein expressions of IRAK1, Myd88 and p65, suggesting that IRAK1 and its related pathways may be one potential mechanism of preventing CAC by Wumei Pill. This study plans to apply Wumei Pills on IRAK1 knockout mice, IRAK1 knockdown and overexpressed HCT116 and Lovo cell lines, with technologies such as ELISA, immunofluorescence, qPCR, and Western Blot, in order to observe the influence of IRAK1 on mice tumorigenesis and the effect of WuMei Pill on IRAK1 and IL-1R/IRAK1/NF-κB/MAPK pathway. We intend to elucidate that IRAK1 may be a key node in CAC pathogenesis and to explain the potential mechanism of preventing CAC by WuMei Pills.