幽门螺杆菌cagA介导CDX2调控Claudin-2在肠型胃癌上皮间质转化中作用及温郁金干预机制的研究

The connections among inflammation、epithelial mesenchymal transformation (EMT) and the tumor and the effects of the traditional Chinese medicine have been increasingly studied recently. Helicobacter pylori cagA ,as the important risk factor in the occurrence and development of gastric cancer, is still not completely clear in terms of its tumorigenic mechanism; the bowel transcription factor Cdx2 and the close connexin Claudin-2 play the necessary role in the process from gastritis to intestinalization, even to the intestinal gastric cancer(EMT process). diterpenoid C , which has been isolated from turmeric ether extracts as a kind of new compounds, can inhibit the release of the inflammation factors in gastric cancer cells and the proliferation of gastric cancer cells, and can induce the apoptosis of gastric cancer cells. Whether there are connections among Helicobacter pylori cagA, Cdx2, Claudin-2 and EMT? What are the connections? Whether diterpenoid C has preventive and therapeutic effect? The cells and animals infected by helicobacter pylori and the nude mouses with transplant tumor will be examined as models. The research will be started with the toxic cell factor cagA, which is known at present as the unique factor encoded by Hp that can be injected into cells, to study the connections among helicobacter pylori cagA, Cdx2, Claudin-2 and gastric cancer EMT and the preventive and therapeutic effect of diterpenoid C. The study will lay the theoretical and experimental basis for the expansion of the horizon of the prevention and control of gastric cancer and the further development and use of the medical value in the traditional Chinese medicine turmeric.

炎症、上皮间质转化（EMT）与肿瘤发生发展的关系及中医药的防治是目前关注的热点。幽门螺杆菌cagA作为胃癌发生发展重要的危险因素其致瘤机制仍未完全明确；在胃炎到肠化、肠型胃癌乃至侵袭转移的过程中，肠转录因子Cdx2、紧密连接蛋白Claudin-2起着不容忽视的作用。我们在郁金醚提物中分离得到新的化合物C，前期研究表明其有抑制胃癌细胞炎症因子释放、细胞增殖和诱导胃癌细胞凋亡等作用。幽门螺杆菌cagA、Cdx2、Claudin-2及EMT之间有否联系？怎样的联系？化合物C是否具有防治作用？我们将通过建立幽门螺杆菌慢性感染的细胞和动物模型及裸鼠移植瘤模型，从Hp编码的目前已知的唯一注入细胞的细胞毒性因子CagA入手，研究幽门螺杆菌cag、Cdx2、Claudin-2与胃癌EMT之间的关系及郁金新二萜类化合物C的防治作用，为拓展胃癌防治视野和中药郁金药用价值的进一步开发和利用奠定理论和实验基础。