使用组蛋白脱乙酰酶抑制剂进行子宫内膜癌化疗的临床前研究。
Preclinical studies of chemotherapy using histone deacetylase inhibitors in endometrial cancer.
作者信息
Takai Noriyuki, Narahara Hisashi
机构信息
Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Hasama-machi, Yufu-shi, Oita 879-5593, Japan.
出版信息
Obstet Gynecol Int. 2010;2010:923824. doi: 10.1155/2010/923824. Epub 2010 Feb 4.
Abstract
Because epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in endometrial 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 endometrial cancer. HDACIs were able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and the expression of genes related to the malignant phenotype in a variety of endometrial cancer cell lines. Furthermore, HDACIs were able to induce the accumulation of acetylated histones in the chromatin of the p21(WAF1) gene in human endometrial carcinoma cells. In xenograft models, some HDACIs have demonstrated antitumor activity with only few side effects. In this review, we discuss the biologic and therapeutic effects of HDACIs in treating endometrial cancer, with a special focus on preclinical studies.
摘要
由于表观遗传改变被认为与子宫内膜癌中肿瘤抑制基因的抑制和肿瘤发生的促进有关，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。在本综述中，我们讨论了HDAC抑制剂（HDACIs）在治疗子宫内膜癌中的生物学和治疗效果。HDACIs能够介导多种子宫内膜癌细胞系中细胞生长的抑制以及细胞周期停滞、凋亡和与恶性表型相关基因的表达。此外，HDACIs能够诱导人子宫内膜癌细胞中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已显示出抗肿瘤活性且副作用很少。在本综述中，我们讨论了HDACIs在治疗子宫内膜癌中的生物学和治疗效果，特别关注临床前研究。
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