组蛋白乙酰化酶(HATs)是催化蛋白乙酰化的关键蛋白酶，其介导的蛋白乙酰化修饰异常与胃癌发生发展密切相关，因此，HATs可能是胃癌防治的一个新的重要靶点。前期在人胃癌组织中成功鉴定了近千种乙酰化修饰蛋白及位点的基础上；通过筛选4406种天然产物中分离的单体化合物，我们发现一种新的HATs抑制剂LXD-070，初步证实其具有抑制胃癌细胞增殖的活性，然而，详细机制尚不清楚。本课题拟系统性研究LXD-070抗胃癌的分子机制。主要聚焦于：①LXD-070对胃癌细胞周期、凋亡的影响及机制；②LXD-070对胃癌细胞蛋白乙酰化调控机制；③LXD-070对胃癌细胞染色质结构的影响。④体内外研究LXD-070通过对乙酰化调控对胃癌进展的影响。通过上述研究揭示HATs抑制剂LXD-070在胃癌蛋白乙酰化修饰异常中所起的关键作用，为胃癌临床治疗提供新的分子靶点；为开发抗胃癌化合物提供理论依据和新思路。

Histone deacetylase (HATs) is a key protease catalyzed acetylation, which is closely related with the development of gastric cancer through mediating aberrent acetylation. Therefore, HATs may be an important new target for prevention and treatment of gastric cancer. In previous study, we isolated a new inhibitor of HATs, LXD-070, from 4406 kinds of natural monomer compounds on the basis of identifing acetylation proteins and sites in human gastric cancer, and we found that LXD-070 significantly inhibited proliferation of gastric cancer cells. However, the detailed mechanism is unclear. Next, we will systematically study the molecular mechanism of LXD-070 against gastric cancer. The topic mainly focus on: ① To investigate the effects of LXD-070 on cell cyle and apoptosis of gastric cancer cell lines, and its mechanisms; ② To explore the regulation mechanism of acetylation for LXD-070 on gastric cancer cell lines; ③ To clear the influence of LXD-070 on gastric cancer cell clines chromatin structure; ④ To illuminate the impact of LXD-070 on the progression of gastric cancer through regulating acetylation in vitro and in vivo. Through the above research, we will reveal the key role played by HATs inhibitor in gastric carcinoma abnormal modification of deacetylases, provide new molecular targets for clinical treatment of gastric cancer; and offer theoretical basis and new ideas for developing anti-tumor compounds.