组蛋白去乙酰化酶抑制剂放射增敏作用与DNA损伤修复机制关系的研究进展

Progress in relationship between histone deacetylase inhibitors-induced radiosensitization and the mechanism of DNA damage repair

组蛋白去乙酰化酶抑制剂(HDACIs)是抑制HDAC活性并造成组蛋白过度乙酰化作用的一类化合物,根据其化学结构的特点,HDACIs化合物被分成短链脂肪酸、异羟肟酸、环肽和苯甲酰胺四大类。研究表明,HDACIs能抑制多种肿瘤细胞的生长,某些具有抗肿瘤作用的HDACIs已经进入临床试验阶段。近年来还发现,HDACIs能增加肿瘤细胞对电离辐射的敏感性,具有较强的放射增敏作用,但该类化合物的放射增敏机制目前还不十分清楚,可能与其能增强肿瘤细胞的凋亡和自噬作用,以及DNA损伤修复机制破坏等有关,其中HDACIs通过导致DNA双链断裂修复机制障碍发挥放射增敏作用已越来越引起学者们的关注。为此,本文就HDACis的放射增敏作用与DNA损伤修复机制之间关系的研究进行综述。

Histone deacetylase inhibitors （HDACIs~ are compounds that can inhibit histone deacetylase^HDAC） while inducing histone hyperacetylation,which are divided into four types： short- chain fatty acid, hydroximic acid, cyclic peptide and benzamide according to chemical structure fea- tures. It has been demonstrated that HDACIs can inhibit the growth of a number of tumor cells, and the study on anti-cancer effects of some HDACIs is in the stage of clinical trials. It has been found that HDACIs can increase the radiosensitivity to tumor cells, indicating that HDACIs may be a potential sensitizer to radiation. The mechanism of HDACIs-induced radiosensitization is still not so clear, which may be related to apoptosis, autophygy or the damage to DNA repair function. And it has been attracting more attention that disrupting DNA repair activity is associated with HDACIs-mediated radiosentization. Thus, research progress in the relationship between HDACIs-mediated radiosentization and the mech- anism of DNA damage repair is reviewed in this paper.