组蛋白去乙酰化酶抑制剂抗肿瘤作用研究进展

Research Progress of Antitumor Effect of Histone Deacetylase Inhibitors

组蛋白去乙酰化酶(histone deacetylase,HDAC)在肿瘤发生和发展的多个环节中扮演着非常重要的角色,如肿瘤抑癌基因沉默、细胞分化、血管生成、细胞迁移、细胞周期异常、信号传导及细胞附着等。组蛋白去乙酰化酶抑制剂(histone deacetylase inhibitors,HDACIs)可以靶向组蛋白去乙酰化酶调控组蛋白的乙酰化,进而调控关键的抑制肿瘤蛋白和原癌基因,是极具潜力的抗肿瘤药物。HDACIs已经在血液/淋巴系统肿瘤治疗方面取得了一定成果,目前已经有2种HDACIs:SAHA(suberoylanilide hydroxamic acid)和FK228被批准用于治疗皮肤T细胞淋巴癌,当前大量的临床试验正在挖掘HDACIs在实体瘤治疗方面的潜力。尽管目前基于细胞的研究发现HDACIs可以诱导肿瘤细胞凋亡,细胞周期抑制,细胞分化,抑制血管生成和自噬等,但HDACIs发挥抗肿瘤活性的分子机制仍未阐明,其对实体瘤的临床治疗效果及相关治疗策略有待进一步确证。

Histone deacetylases（histone deacetylase, HDAC） plays a very important role in initiation and progress of cancer, such as the silence of tumor suppressor gene, cell differentiation, angiogenesis, cell migration, cell cycle abnormality, signal transduction and cell adhesion. Histone deacetylase inhibitors（HDACIs） which may target histone deacetylase and regulate histone acetylation, and then regulate key suppressor proteins and proto-oncogene, have great potential in being anti-cancer drugs. HDACIs have made achievements in treatment of hematological malignances. There are already 2 HDACIs（SAHA and FK228） have been approved for the treatment of cutaneous T-cell lymphoma. A large number of clinical trials currently are being excavated in HDACIs potential treatment of solid tumors. Although cell research based on the discovery HDACIs can induce tumor cell apoptosis, cell cycle inhibition, cell differentiation, inhibition of angiogenesis and autophagy, etc., but HDACIs exert anti-tumor activity of the molecular mechanisms remain unclear, the clinical treatment of solid tumors effects and related treatment strategies needs to be further confirmed.