Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Oita 879-5593, Japan.
J Oncol. 2010;2010:458431. doi: 10.1155/2010/458431. Epub 2009 Dec 20.
Since epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in ovarian cancers, novel compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach. In this review, we discuss the biologic and therapeutic effects of HDAC inhibitors (HDACIs) in treating ovarian cancer. HDACIs were able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and expression of genes related to the malignant phenotype in a variety of ovarian cancer cell lines. Furthermore, HDACIs were able to induce the accumulation of acetylated histones in the chromatin of the p21(WAF1) gene in human ovarian carcinoma cells. In xenograft models, some of HDACIs have demonstrated antitumor activity with only few side effects. Some clinical trials demonstrate that HDACI drugs provide an important class of new mechanism-based therapeutics for ovarian cancer. In this review, we discuss the biologic and therapeutic effects of HDACIs in treating ovarian cancer, especially focusing on preclinical studies and clinical trials.
由于表观遗传改变被认为参与了卵巢癌中肿瘤抑制基因的抑制和肿瘤发生的促进，因此具有组蛋白去乙酰化酶（HDAC）抑制活性的新型化合物是一种有吸引力的治疗方法。在这篇综述中，我们讨论了 HDAC 抑制剂（HDACIs）在治疗卵巢癌中的生物学和治疗作用。HDACIs 能够在多种卵巢癌细胞系中介导对细胞生长、细胞周期停滞、细胞凋亡和与恶性表型相关的基因表达的抑制。此外，HDACIs 能够诱导人类卵巢癌细胞中 p21（WAF1）基因染色质中乙酰化组蛋白的积累。在异种移植模型中，一些 HDACIs 表现出抗肿瘤活性，且副作用较少。一些临床试验表明，HDACI 药物为卵巢癌提供了一类重要的基于新机制的治疗药物。在这篇综述中，我们讨论了 HDACIs 在治疗卵巢癌中的生物学和治疗作用，特别是侧重于临床前研究和临床试验。
