峨参提取物通过STAT3通路抑制结肠癌炎性微环境的作用及机制

There is high incidence and high mortality in　colon cancer，which persistent inflammatory microenvironment is an important risk factor for the growth and progression. How to regulate and control the inflammatory signal is the key factor to the success of treatment. Signal transducers and activators of transcription 3(STAT3) is a key molecule in the formation of tumor associated inflammation. Inhibitory activity of STAT3 can effectively inhibit tumor development. According to Traditional Chinese medicine, invigorating spleen can improve inflammatory microenvironment of colon cancer. Anthriscus sylvestris has the function of invigorating spleen. Our previous study found that Anthriscus sylvestris extract can inhibit effect on cell proliferation and can effectively inhibit the abnormal activation of STAT3 in colon cancer. But its specific inhibitory effect and molecular mechanism is not clear. We hypothesis: Anthriscus sylvestris extract can inhibit inflammatory microenvironment through the STAT3 signaling pathway, and then inhibit cell proliferation of colon cancer..Based on this, this project intends to do these. Establishment of a mouse model of colitis associated colon cancer which can simulate inflammatory microenvironment of colon cancer in vivo. Light microscope and electron microscope were used to observe the changes of tissue structure. Detection of STAT3 and STAT3 phosphorylated expression in tissues by Western blotting. This topic is to explore the mechanism of Anthriscus sylvestris extract inhibition effect on inflammatory microenvironment of colon cancer. Furthermore, it should be established an inflammatory response model of HT29 cells which can simulate inflammatory microenvironment of colon cancer in vitro. Using specific inhibitors or interference techniques to alter target gene expression, And to investigate Anthriscus sylvestris extract inhibition effect on inflammatory microenvironment of colon cancer. And it would explain the molecular mechanism whether through STAT3 signaling pathway and upstream JAK, SHP regulation, and explain Anthriscus sylvestris extract whether could block or inhibit STAT3 activity induced by IL-6. This study will provide a new strategy and scientific basis for the anti-tumor of traditional Chinese medicine.

结肠癌高发且死亡率居高不下，其持续的炎性微环境是促进肿瘤进展重要危险因素，抑制其炎症信号是治疗成功的关键。STAT3是肿瘤相关性炎症形成中的关键分子，抑制其活性可抑制肿瘤进展。中医认为健脾中药能改善肠癌炎性微环境。峨参能健脾，且我们前期研究发现峨参提取物能抗结肠癌增殖、有效抑制STAT3活化，但作用机制尚不清楚。我们假说：峨参通过抑制STAT3信号抑制结肠癌炎性微环境进而抑制其增殖。.基于此，本项目拟构建肠炎相关结肠癌小鼠模型模拟体内炎性微环境，光镜及电镜观察组织结构改变，Western印迹法检测组织中STAT3及磷酸化表达，探讨峨参对结肠癌炎性微环境的抑制作用及机制；同时构建细胞炎性反应模型，利用抑制剂或干扰技术，探讨峨参对结肠癌炎性微环境的抑制作用，及其是否通过STAT3及上游JAK、SHP调控，及其能否阻断或抑制IL-6诱导的STAT3活性。本研究将为中药抗肿瘤提供新策略和科学依据。

结肠癌高发且死亡率居高不下，其持续的炎性微环境是促进肿瘤进展重要的危险因素，如何抑制其炎症信号是治疗成功的关键。STAT3是肿瘤相关性炎症形成中的关键分子，抑制其活性可抑制肿瘤进展。中医认为健脾中药能改善肠癌炎性微环境。峨参能健脾，且我们前期研究发现峨参提取物能抗结肠癌增殖、有效抑制STAT3异常活化，但作用机制尚不清楚。我们假说：峨参提取物能通过抑制STAT3信号抑制结肠癌炎性微环境进而抑制其增殖。.基于此，本项目拟构建肠炎相关结肠癌小鼠模型模拟结肠癌的体内炎性微环境，显微观察肠黏膜组织结构改变，Western印迹法检测组织中JAK、SHP、STAT3及磷酸化表达，从整体动物水平探讨峨参提取物对结肠癌炎性微环境的抑制作用，并从STAT3信号通路探讨其机制；同时构建结肠癌HT29细胞炎性反应模型，利用抑制剂或干扰技术，从细胞分子水平探讨峨参提取物对结肠癌炎性微环境的抑制作用，并探讨其作用机制是否通过STAT3及上游信号JAK、SHP家族调控，以及峨参提取物能否阻断或抑制由IL-6 诱导的STAT3 活性，最终探明其作用机制是否通过IL-6/JAK/STAT3信号通路而抑制结肠癌炎性微环境。本研究将为中药抗肿瘤提供新策略和科学依据。.通过本课题研究可以得出结论：峨参提取物通过IL-6/JAK/STAT3通路抑制结肠癌炎性微环境，进而抑制肿瘤增殖。