肝细胞肝癌是恶性程度很高的肿瘤，其恶性增殖是临床治疗失败的原因之一。寻找有效的抑制肿瘤增殖药物，是肝癌治疗的一条重要途径。我们前期的药物筛查发现，天然化合物Dalbinol能有效抑制肝癌细胞HepG2，HepG2/ADM和SMMC-7721生长；进一步研究发现Dalbinol通过上调Wnt通路的负向调节因子DACH1，从而抑制Wnt通路激活。但Dalbinol的直接靶点尚不清楚。我们假设：Dalbinol通过某种机制上调DACH1，进而抑制β-catenin介导的肝癌细胞增殖。本项目拟采用亲和层析和质谱技术，寻找Dalbinol的直接靶点，并探索该靶点与DACH1/β-catenin通路的关系；拟通过人源肝癌组织的异体移植模型，证实Dalbinol的体内抗肿瘤活性。本项目的完成将会阐明Dalbinol抑制肝癌增殖的分子机制，为肝癌的治疗更有效的候选化合物。

Hepatocellular carcinoma is a high malignant tumor，and one of the leading cause of treatment failure is malignant proliferation. Compound screening manifested that rotenoid Dalbinol suppressed cell growth in HepG2, HepG2/ADM and SMMC-7721 cells. Further exploration showed that Dalbinol suppressed Wnt signaling by promoting the expression of DACH1，which was a negative modulator of Wnt pathway. However, the direct target of Dalbinol is not clear yet. Basis on information above, we put forward this hypothesis: Dalbinol suppressed cell growth through DACH1/β-catenin axis. Here, we will look for the direct target of Dalbinol by affinity chromatography and mass spectrometry, and explore the relationship between the two. Also, we will confirm the antitumor activity of Dalbinol in vivo by patient-derived tumor tissue xenograft models. In all, this project will reveal the mechanism of how Dalbinol inhibit cell proliferation through DACH1/β-catenin axis in HCC cells, and provide a new candidate compound for HCC therapy.