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摘要
卵巢上皮癌是妇科恶性肿瘤死亡的主要原因。治疗卵巢癌,特别是在耐药的情况下,我们需要更好的治疗卵巢癌患者的新的有潜力的药剂。表观遗传事件,如DNA甲基化和组蛋白修饰的变化,通过其对核酸蛋白的相互作用,染色质构象和基因的表达,影响细胞功能,癌症表征,临床现象,以及最终结果。先前的研究表明,在血液和一些肿瘤细胞中,组蛋白去乙酰化酶(HDAC)抑制剂有较强的细胞生长抑制和凋亡活性。Oxamflatin,含有芳香磺酰胺和异羟肟酸基团的化合物,被称为是一种能够抑制小鼠和人类肿瘤细胞株生长的有效的HDAC抑制剂。在这项研究中我们发现,Oxamflatin 纳米级可以在OVCAR-5 和 SKOV-3 卵巢癌细胞株引起形态学改变。用Oxamflatin治疗也导致细胞活力有所下降。此外,BrdU掺入法检测,细胞计数和 Ki-67 免疫组织化学染色的结果表明Oxamflati能够显著抑制DNA合成和细胞增殖。采用实时定量PCR法和西方 blot分析发现Oxamflatin能够下调 c-Myc, CDK4, E2F1和Rb蛋白的磷酸化水平的表达,但能上调p21。这些研究结果对检验在对体内卵巢癌的抗癌作用中,Oxamflati和/或与其它试剂的组合是否产生作用铺平了道路。
关键词: oxamflatin,HDAC抑制剂、卵巢癌、表观遗传学、细胞周期、组蛋白乙酰化。
Current Molecular Medicine
Title:HDAC Inhibitor Oxamflatin Induces Morphological Changes and has Strong Cytostatic Effects in Ovarian Cancer Cell Lines
Volume: 16 Issue: 3
Author(s): Y.-L. Wang, H.-L. Liui, R.-G. Fu, Z.-W. Wang, H.-T. Ren, Z.-J. Dai, Y.-Y. Jing and Y. Li
Affiliation:
关键词: oxamflatin,HDAC抑制剂、卵巢癌、表观遗传学、细胞周期、组蛋白乙酰化。
摘要: Ovarian epithelial carcinoma is the leading cause of deaths from gynecologic malignancy. New reagents with therapeutic potentials against ovarian cancer, especially the drug-resistant cases, are required for better treatment of ovarian cancer patients. Epigenetic events such as changes in DNA methylation and histone modification, through their effects on DNA-protein interaction, chromatin conformation, and gene expression, affect cell function, cancer behavior, clinical manifestations, and outcomes. Previous studies have shown that histone deacetylase (HDAC) inhibitors have strong cytostatic and apoptotic activities in hematologic and some solid cancer cells. Oxamflatin, a compound containing the aromatic sulfonamide and hydroxamic acid groups, is known to be a potent HDAC inhibitor capable of inhibiting the growth of mouse and human cancer cell lines. In this study we found that oxamflatin in the nM range induced morphological changes in OVCAR-5 and SKOV-3 ovarian cancer cell lines. Treatment with oxamflatin also led to decreased cell viability. Moreover, results of BrdU incorporation assay, cell counting, and Ki-67 immunostaining indicated that oxamflatin was able to significantly inhibit DNA synthesis and cell proliferation. Using real-time PCR and Western blot analyses we demonstrated that oxamflatin was capable of downregulating the expression of c-Myc, CDK4, E2F1, and the phosphorylation levels of Rb protein, but upregulating p21. These findings pave the way to examine if oxamflatin along with or in combination with other reagents could deliver anticancer effects against ovarian cancers in vivo.
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Cite this article as:
Y.-L. Wang, H.-L. Liui, R.-G. Fu, Z.-W. Wang, H.-T. Ren, Z.-J. Dai, Y.-Y. Jing and Y. Li , HDAC Inhibitor Oxamflatin Induces Morphological Changes and has Strong Cytostatic Effects in Ovarian Cancer Cell Lines, Current Molecular Medicine 2016; 16 (3) . https://dx.doi.org/10.2174/1566524016666160225151408
DOI https://dx.doi.org/10.2174/1566524016666160225151408 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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