AD20是我们从天然产物库中筛选的单体化合物，它抑制肿瘤的生长（高剂量）、转移及血管生成。我们采用全蛋白质组学、网络药理学和初步的实验显示，AD20能抑制EZH2/SIRT7相关通路及其相互作用和NRP1的表达。作为表观遗传学的调节者，EZH2诱导H3K27的甲基化从而沉默一些肿瘤抑制基因，SIRT7促进H3K18的去乙酰化诱导肿瘤侵袭和转移，它们也通过非表观遗传学途径影响肿瘤的发生发展。本项目拟阐明AD20对EZH2/SIRT7的调节与抑制前列腺癌转移和血管生成的关系；研究AD20对EZH2与SIRT7相互作用的影响以及microRNA与它们的串话调节；包括可能的上下游途径，如GSK3β在介导AD20调节EZH2中的作用，EZH2/β-catenin复合体对下游分子如NRP1的调节等，确定AD20调节的肿瘤表观遗传学和非表观遗传学网络和靶点，为未来肿瘤防治药物的研究提供线索和思路。

AD20 is a single compound which we have screened from a natural products library. We found it could inhibit tumor growth (at high dose), metastasis and angiogenesis. By using the whole proteomics, network pharmacology and preliminary experiments approaches, we found that AD20 could inhibit the expression and interaction of EZH2 / SIRT7 pathway, and the expression of NRP1. As epigenetic mediator, EZH2-induced H3K27 methylation, thereby silencing some tumor suppressor gene, SIRT7 promote H3K18 deacetylation and induce tumor invasion and metastasis, they also affect tumorigenesis through non epigenetic pathways. The proposed study intends to clarify the role of EZH2 / SIRT7 on AD20 inhibited prostate cancer metastasis and angiogenesis; the interaction between EZH2 and SIRT7, the crosstalk with microRNA induced by the treatment of AD20; study the possible downstream pathways, including GSK3β in mediating EZH2's role, the downstream molecules of EZH2 / β-catenin complex such as NRP1. Expect our work can clarify the epigenetic and non-epigenetic network and potential targets regulated by AD20 and provide clues and ideas for future anticancer drugs study.