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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2.5~20μmol/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。
Acetylation modification is a biologically significant post-translational modification of proteins. It is catalyzed by histone acetyltransferase (HAT) and histone deacetylase (HDAC). Recently, it has been found that HDAC inhibitors can regulate angiogenesis by inhibiting the proliferation of endothelial cells. However, it is unclear whether HAT inhibitors have the opposite effect. This study investigated the effect of HAT inhibitor Garcinol on proliferation, apoptosis, migration and tube formation of human umbilical vein endothelial cells cultured in vitro. The results showed that Garcinol reduced the number of viable cells in HUVEC in a dose-dependent manner in the range of 2.5 ~ 20μmol / L. Garcinol treatment had no significant effect on the cell cycle of HUVEC. However, Hochest staining, TUNEL staining and flow cytometry showed that Garcinol treatment significantly induced apoptosis of HUVEC. In addition, Garcinol treatment also inhibited HUVEC migration and tube formation in vitro. The above results suggest that HAT inhibitors may inhibit angiogenesis by inducing endothelial cell apoptosis, which may be a new mechanism of antitumor effect.