枫蓼肠胃康经IL-6/STAT3-PXR双向通路增效5-FU治疗结肠炎相关性结肠癌的作用及机制研究

5-FU为治疗结肠炎相关性结肠癌（CACC）的首选化疗药，常由于化疗效率低下及易发生耐药而降低治疗效果。IL-6 介导的STAT3通路激活可以诱发CACC，核受体PXR可反向调控IL-6/STAT3通路而抑制CACC。我们前期研究发现FLCWK可抑制IL-6、STAT3表达，并能协同5-FU促结肠癌细胞凋亡；同时发现FLCWK虽可激活PXR转录调控，但却体现出抑制P-gp的作用。由此提出FLCWK可通过IL-6/STAT3-PXR双向通路增效5-FU，同时经IL-6/STAT3通路消除PXR对P-gp激活介导的5-FU耐药，发挥PD-PK协同增效作用。本课题拟借助CACC小鼠模型、PXR及STAT3不同表达水平的细胞模型进行药效学及药动学研究，获得枫蓼肠胃康经IL-6/STAT3-PXR 通路双向调控增效5-FU治疗CACC的证据，为发现安全有效的CACC化疗辅助药物提供数据支持。

5-FU is the preferred chemotherapeutic agents for colitis-associated colorectal cancer (CACC) treatment, however its chemotherapy effect usually decreases because of drug resistance caused by low chemotherapy efficiency. Activation of STAT3 pathway mediated by IL-6 could induce the conversion of colitis to colon cancer, and the reverse regulation of PXR on IL-6-STAT3 pathway could inhibit CACC. Previous pharmacodynamics research found that Feng-liao- chang-wei-kang could both function as an anti-gastroenteritis drug by inhibiting IL-6 and STAT3 expression, and also as a synergism drug of 5-FU by promoting early apoptosis of colon cancer cells. Previous pharmacokinetic study found that under the condition of colitis, Feng-liao- chang-wei-kang could induce PXR expression but inhibit P-gp expression. Therefore we propose that Feng-liao-chang-wei-kang can play a role of PD-PK related synergy with 5-FU via IL-6/STAT3- PXR bi-directional pathways. By using pharmacodynamics and pharmacokinetic study models including CACC model and different PXR，STAT3 expression cell models, this study intends to get the evidence of Feng-liao-chang-wei-kang’ s synergistic effect with 5-FU treatment on CACC, via bidirectional regulation on IL-6/STAT3-PXR pathways, which supplies data supports to find a safe and efficient adjuvant chemotherapy of CACC.