Garmpis Nikolaos, Damaskos Christos, Garmpi Anna, Georgakopoulou Vasiliki E, Sarantis Panagiotis, Antoniou Efstathios A, Karamouzis Michalis V, Nonni Afroditi, Schizas Dimitrios, Diamantis Evangelos, Koustas Evangelos, Farmaki Paraskevi, Syllaios Athanasios, Patsouras Alexandros, Kontzoglou Konstantinos, Trakas Nikolaos, Dimitroulis Dimitrios
Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
N.S. Christeas Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
J Pers Med. 2021 Mar 22;11(3):223. doi: 10.3390/jpm11030223.
Hepatocellular carcinoma (HCC) remains a major health problem worldwide with a continuous increasing prevalence. Despite the introduction of targeted therapies like the multi-kinase inhibitor sorafenib, treatment outcomes are not encouraging. The prognosis of advanced HCC is still dismal, underlying the need for novel effective treatments. Apart from the various risk factors that predispose to the development of HCC, epigenetic factors also play a functional role in tumor genesis. Histone deacetylases (HDACs) are enzymes that remove acetyl groups from histone lysine residues of proteins, such as the core nucleosome histones, in this way not permitting DNA to loosen from the histone octamer and consequently preventing its transcription. Considering that HDAC activity is reported to be up-regulated in HCC, treatment strategies with HDAC inhibitors (HDACIs) showed some promising results. This review focuses on the use of HDACIs as novel anticancer agents and explains the mechanisms of their therapeutic effects in HCC.
肝细胞癌（HCC）仍然是一个全球性的重大健康问题，其患病率持续上升。尽管引入了多激酶抑制剂索拉非尼等靶向治疗方法，但治疗效果并不理想。晚期HCC的预后仍然很差，这凸显了对新型有效治疗方法的需求。除了导致HCC发生的各种危险因素外，表观遗传因素在肿瘤发生中也发挥着功能性作用。组蛋白脱乙酰酶（HDACs）是一种能从蛋白质（如核心核小体组蛋白）的组蛋白赖氨酸残基上去除乙酰基的酶，这样就不允许DNA从组蛋白八聚体上松开，从而阻止其转录。鉴于据报道HDAC活性在HCC中上调，使用HDAC抑制剂（HDACIs）的治疗策略显示出一些有前景的结果。本综述重点关注HDACIs作为新型抗癌药物的应用，并解释其在HCC中的治疗作用机制。
