Wnt/β-catenin信号通路参与细胞增殖分化和基因表达等重要生物过程。该通路中的多个成员都与乳腺癌的发生、发展密切相关。达玛烷三萜对乳腺癌细胞增殖有显著的抑制作用，但相关研究多集中于凋亡通路，其调控Wnt/β-catenin通路却鲜有报道。申请人前期首次从葫芦科植物绞股蓝中分离得到具有显著抑制乳腺癌细胞增殖的A环为七元环的新型达玛烷三萜，初步发现它们的作用机制与Wnt/β-catenin通路相关。本课题拟采用Wnt/β-catenin通路为筛选模型，通过蛋白追踪法，并运用多种现代光谱技术和化学反应，对绞股蓝中结构新颖的达玛烷三萜进行系统分离；通过Wnt/β-catenin通路下游蛋白C-myc等的表达水平评价其抗乳腺癌活性；深入探讨结构新颖的达玛烷三萜与抑制乳腺癌细胞增殖的构效关系；以乳腺癌异种移植小鼠为研究对象，对这类成分进行分子生物学机制研究，以期发现高效低毒的抗肿瘤先导化合物。

Wnt/β-catenin pathway has been proposed as an important pathway for breast cancer metastasis and therapy prognosis. Dammarane-type triterpenes showed notable activities against breast cancer cell proliferation. However, research on its inhibitory mechanism mostly focused on the apoptosis pathway, whereas its effect on Wnt/β-catenin pathway regulation is rarely reported. Our previous chemical investigation on Gynostemma pentaphyllum resulted into the isolation of a series of dammarane-type triterpenes which possess the unprecedented skeleton of ring A and with notable activity on breast cancer cell lines. Preliminary mechanism study showed that this effect is associated with the Wnt/β-catenin pathway. This study aims to screen biological dammarane-type triterpenes from Gynostemma pentaphyllum by using established Wnt/β-catenin pathway screening model with protein tracking method and assistance of modern spectrum techniques and chemical reaction. The expression of C-myc, CyclinD1 and Survivin in the downstream of Wnt/β-catenin pathway was used to evaluate the anti breast cancer activity. The structure activity relationships between novel dammarane-type triterpenes and inhibited breast cancer cells proliferation were discussed. By using human breast cancer xenograft mice, the anti-breast cancer effects and the underlying mechanisms of those compounds will be further evaluated. This project is planning to discover the new anti-tumor lead compounds against breast cancer.