论文部分内容阅读
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 deacetylase (HDAC) plays a very important role in many aspects of tumorigenesis and development, such as tumor suppressor gene silencing, cell differentiation, angiogenesis, cell migration, abnormal cell cycle, signal Conduction and cell attachment. Histone deacetylase inhibitors (HDACIs) target histone deacetylases and regulate the acetylation of histone proteins, thereby regulating the key suppressor of tumor proteins and proto-oncogenes. It is a potential anti-tumor drug. HDACIs have achieved some results in the treatment of hematologic / lymphatic system oncology. There are currently two HDACIs: SAHA (suberoylanilide hydroxamic acid) and FK228 approved for the treatment of cutaneous T-cell lymphoma. Currently, a large number of clinical trials are exploring HDACIs Solid tumor treatment potential. Although currently cell-based studies have found HDACIs can induce tumor cell apoptosis, cell cycle inhibition, cell differentiation, inhibition of angiogenesis and autophagy, the molecular mechanism of HDACIs antitumor activity remains unclear, and its clinical treatment of solid tumors Effect and related treatment strategies need further confirmation.