作为阿尔茨海默病发生的共性基因淀粉样前体蛋白（APP）和中性内肽酶（NEP）在肿瘤的异常表达与肿瘤的发生、侵袭、转移、耐药等有着密切的关系。预实验结果表明组蛋白修饰介导了APP高表达，与肿瘤生长有着直接关系。EGCG具有抑制组蛋白去乙酰化酶（HDAC1）表达的作用。我们其它项目研究证实EGCG促进AD模型小鼠的学习和认知能力的改善，与激活NEP表达有关。同时EGCG具有下调APP的作用，但在AD和肿瘤中分别呈现的是神经细胞保护和诱导肿瘤细胞凋亡截然相反的作用。本项目拟从细胞和整体水平通过正、反实验论证肿瘤中NEP沉默及APP高表达之间的关系；明确EGCG调控APP代谢诱导肿瘤细胞凋亡的表观遗传学机制，阐明EGCG作为HDAC抑制剂对肿瘤细胞高度靶向性的物质基础；对比分析HDAC1介导EGCG调控APP-NEP信号通路的串话在肿瘤和AD中的差异，为EGCG的抗肿瘤及AD治疗提供充分理论依据。

As the common genes of pathogenesis of Alzheimer's disease, the abnormal expressions of amyloid precursor protein (APP) and neprilysin (NEP) are close relate to tumor occurrence, invasion, metastasis and drug resistance. Our preliminary experimental results indicated that histone modification mediated the high expression of APP, and promoted tumor growth. We and others have shown the inhibitory activity of EGCG on HDAC1. Our previous project verified that EGCG attenuates cognitive deterioration in AD mice by up-regulation NEP expression. Meanwhile, EGCG down-regulated APP expression both in AD and tumor, however, presented the opposite effects which were neuron protection and cellular apoptosis induction, respectively. The positive and negative arguments will be employed by in vivo and in vitro experiments. The present study aims to investigate the relationship between NEP silence and APP over-expression, and the epigenetic mechanism in which EGCG regulates the metabolism of APP and induces tumor cell apoptosis. Moreover, the targets on cancer cell of EGCG which acts as HDAC inhibitor will also be clarified. Furthermore, compare the different and crosstalk of APP-NEP signal pathway mediated by HDAC1 in AD and tumor under the treatment of EGCG, and provide sufficient theoretical foundation for anti-tumor and AD therapy.