组蛋白去乙酰化酶抑制剂对神经胶质瘤的作用研究

Research on Histone Deacetylase Inhibitors in Glioma

正常细胞的分化以及代谢行为的调节依赖组蛋白乙酰基转移酶和组蛋白去乙酰化酶之间的平衡。一旦这种平衡关系被打破,细胞或组织就容易发生癌变,神经胶质瘤也不例外。神经胶质瘤是一种恶性度高且预后极差的颅内肿瘤,其作用机制尚不明确且呈浸润性生长。因此在治疗手段方面尚无行之有效的方法。组蛋白去乙酰化酶抑制剂作为一种新型的化疗药物为胶质瘤的治疗提供了新的方向。它通过阻碍细胞周期、诱导细胞分化和凋亡以及抑制肿瘤血管生成来抑制神经胶质瘤的生长和增殖。本文旨在从化学结构特点和对神经胶质瘤作用机制两方面阐述组蛋白去乙酰化酶抑制剂,并对新的一类组蛋白去乙酰化酶抑制剂丙戊酸及其衍生物的研究作一综述。

The balance between histone acetyhransferases （HATs） and histone deacetylases （HDACs） regulates normal cell differentiation and metabolism activity. Disturbance of the balance between HATs and HDACs can lead to cancers including gliomas. Glioblastoma （GBM） is a malignant tumor in central nervous system and the prognosis of patients with GBM is poor. The mechanism of gliomagenesis is still unknown., Histone deacetylase inhibitors （HDACI） was proven to inhibit gliomas cell growth and proliferation via various mechnisms,including cell cycle arrest, induction of cell differentiation and apoptosis, as well as inhibition of angiogenesis. In this article, we introduced HDACIs from the point of chemical structure and the mechanism of anti-glioma. ,We also reviewed the literatures of and valproic acid and its derivatives.