上皮间质转化（EMT）在肿瘤侵袭转移过程中发挥着关键作用，而TGF-β是目前研究最为深入的EMT诱导因子。前期研究发现，草苁蓉环烯醚萜苷抑制小鼠肝癌移植瘤血管生成，调节MMP/TIMP比值降低大鼠肝脏癌前病变组织ECM沉积，体外抑制肝癌细胞迁移和EMT发生。这些过程中均发现草苁蓉环烯醚萜苷下调TGF-β1表达。提示，草苁蓉环烯醚萜苷可通过介导TGF-β通路调控EMT抑制肝癌侵袭转移。本项目拟以TGF-β介导的EMT为切入点，探讨TGF-β通路在肝癌细胞EMT过程中的角色地位，以及此过程中TGF-β/Smad经典通路与PI3K/Akt/GSK-3β通路的交叉对话，为肝癌侵袭转移调控提供可能靶标；揭示草苁蓉环烯醚萜苷介导TGF-β调控肝癌细胞EMT的分子机制，确定其靶向调控EMT的确切靶标，阐明其介导TGF-β通路调控EMT抑制肝癌侵袭转移的机制和作用特点。本项目将为肝癌防治策略提供新的途径。

Epithelial-mesenchymal transition (EMT) plays a key role in tumor invasion and metastasis, and TGF-β is the most thoroughly studied EMT-inducing factor. Our previous studies found that Boschniakia rossica iridoid glycosides inhibit angiogenesis of transplanted hepatocarcinoma tissue in mice, reduce the ECM deposition of hepatic preneoplastic lesions via regulation of MMP/TIMP ratio in rats, and inhibit the migration and EMT of hepatoma cells in vitro. In these processes, the expression of TGF-β is down-regulated by Boschniakia rossica iridoid glycosides. The results suggest that Boschniakia rossica iridoid glycosides may inhibit the invasion and metastasis of hepatocellular carcinoma by TGF-β-mediated regulation of epithelial-mesenchymal transition. Therefore, this project is intended to further explore the role of TGF-β pathway and the cross-talk between TGF-β/Smad classic pathway and PI3K/Akt/GSK-3β pathway in EMT process of hepatocellular carcinoma and provide a possible target for the regulation of invasion and metastasis of hepatocellular carcinoma; reveal the molecular mechanism of Boschniakia rossica iridoid glycosides for the TGF-β-mediated regulation of EMT, determine the exact target for the regulation of EMT in hepatocellular carcinoma, and clarify the inhibitory mechanisms and characteristics of Boschniakia rossica iridoid glycosides on invasion and metastasis of hepatocellular carcinoma by TGF-β-mediated regulation of EMT. This project will enrich the medicinal connotation of Boschniakia rossica, and provide a new strategy for the prevention and treatment of liver cancer.