中文摘要：

乙酰化（acetylation）修饰是具有重要生物学意义的蛋白质翻译后修饰方式，由相互拮抗的组蛋白乙酰转移酶（histone acetyltransferase，HAT）和组蛋白去乙酰化酶（histone deacetylase，HDAC）所催化。近期发现HDAC抑制剂可通过抑制内皮细胞增殖等方式调节血管新生（angiogenesis），但HAT抑制剂是否有相反效应尚不明确。本研究观察了HAT抑制剂Garcinol对体外培养的人脐静脉内皮细胞HUVEC增殖、凋亡、迁移及成管的影响。结果发现，Garcinol在2．5～20＆mol／L的范围内可剂量依赖性减少HUVEC的活细胞数目。Garcinol处理对HUVEC的细胞周期无明显影响，但Hochest染色、TUNEL染色及流式细胞术均发现Garcinol处理可显著诱导HUVEC的凋亡。此外，Garcinol处理还可抑制HUVEC的迁移和体外成管。以上结果提示：HAT抑制剂可能通过诱导内皮细胞凋亡而抑制血管新生，这可能是其抗肿瘤效应的新机制。

英文摘要：

A cetylation is an post-translational modification of important biological significance. Acetylation modification is catalyzed by the antagonistic histone acetyltransferase （HAT） and histone deacetylase （HDAC）. Recent studies found that the HDAC inhibitors regulated angiogenesis via suppressing the proliferation of endothelial cells, but whether HAT inhibitor had opposite effects was unknown. In the present study, the potential effects of the HAT inhibitor Garcinol on the proliferation, apoptosis, migration and tuber formation of HUVEC in vitro were investigated. The results indicated that Garcinol of2.5-20μmol/L could reduce the survival of HUVEC in a dose-dependent manner. Treatment with Garcinol had no obvious effect on the cell cycle of HUVEC, but it significantly induced apoptosis of HUVEC, as evidenced by the experimental data from Hochest staining, TUNEL examination and flow cytometry. In addition, treatment with Garcinol suppressed the migration and the in vitro tuber formation of HUVEC. These data suggested the HAT inhibitor might suppress angiogenesis via inducing endothelial apoptosis, which might represent the novel mechanism of anti-tumor activity.