Histone 英 /'hɪstəʊn/ 美 /'hɪston/
释 义 n. [生化] 组蛋白
例 句 The changes of epigenetics such as DNA methylation and histone modification can regulate the expression of genes and play an important role in the development of tumors. 表观遗传学改变，如DNA甲基化和组蛋白修饰改变可以调控基因的表达，在肿瘤的发生和发展中可能起关键作用。
释 义 n. 脱乙酰酶；去乙酰酶
例 句 Indeed, HDAC6 deacetylates various substrates including α-tubulin and HSP90α, and is involved in protein trafficking and degradation, cell shape and migration. 事实上，HDAC6可以α-微管蛋白和HSP90α进行去乙酰化，与蛋白质转运、降解、细胞形状和迁移都有关系。
作者： Richard S. Laschanzky
Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of <10% due in part to a lack of effective therapies. Pan-histone deacetylase (HDAC) inhibitors have shown preclinical efficacy against PDAC but have failed in the clinic due to toxicity. Selective HDAC inhibitors may reduce toxicity while retaining therapeutic efficacy. However, their use requires identification of the specific HDACs that mediate the therapeutic effects of HDAC inhibitors in PDAC. We determined that the HDAC1/2/3 inhibitor Mocetinostat synergizes with the HDAC4/5/6 inhibitor LMK-235 in a panel of PDAC cell lines. Furthermore, while neither drug alone synergizes with gemcitabine, the combination of Mocetinostat, LMK-235, and gemcitabine showed strong synergy. Using small interfering (si)RNA-mediated knockdown, this synergy was attributed to inhibition of HDACs 1, 2, and 6. Pharmacological inhibition of HDACs 1 and 2 with Romidepsin and HDAC6 with ACY-1215 also potently synergized with gemcitabine in a panel of PDAC cell lines, and this drug combination potentiated the antitumor effects of gemcitabine against PDAC xenografts in vivo. Collectively, our data show that inhibition of multiple HDACs is required for therapeutic effects of HDAC inhibitors and support the development of novel strategies to inhibit HDACs 1, 2, and 6 for PDAC therapy.