上皮间质转化（EMT）是胃癌远端转移的重要生物学过程。前期研究发现，中药提取物南蛇藤总萜可明显抑制胃癌细胞EMT进程，从而抑制胃癌侵袭、迁移的发生。经蛋白质组学分析，EMT上游的关键调控蛋白丝切蛋白1（cofilin 1）在南蛇藤总萜作用前后的表达差异性最为显著，但cofilin 1参与南蛇藤总萜抑制胃癌EMT发生的分子机制尚不清楚。本项目拟结合体内外研究，探讨南蛇藤总萜靶向cofilin 1蛋白，通过Rac1 - ROCK1/ PAK1 - LIMK1及SSH信号通路抑制胃癌细胞侵袭和迁移的分子机制，为开发生物利用度高的抗癌新药奠定基础。

Epithelial-to-mesenchymal transition (EMT), the process of cells losing their epithelial phenotype and acquiring a migratory mesenchymal phenotype, has been accepted to play an important role in cancer metastasis in several human malignancies including gastric cancer. Previous studies was performed to investigate the inhibitory effects of Celastrus orbiculatus (COE) on the invasion and migration of human gastric cancer cells in vitro. Recently, using a comparative proteomics approach, the target-specific proteins were identified as differently expressed, with cofilin1 being one of the most significantly down-regulated proteins induced by COE (2.5-fold down-regulation). Therefore, we selected cofilin1 for further study. In this study, we investigated the role of cofilin1 in COE-mediated inhibition of EMT and tumor metastasis in vivo. We also investigated the interaction between Rac1-Rho kinase (ROCK)1/p21-activated kinase (PAK)1-LIM kinase (LIMK)1 and Slingshot (SSH) signaling pathway in controlling metastatic potential of gastric cancer cells and explored the underlying molecular mechanism by which COE modulates the EMT-mediated alteration of human gastric cancer cells. These findings reveal that application of COE in treating metastatic gastric cancer boasts promising prospect and will become potential therapy all over the world.