期刊
JOURNAL OF HEPATOLOGY
卷 50, 期 3, 页码 518-527出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2008.10.022
关键词
Aurora kinases; Hepatocellular carcinoma; Small-molecule inhibitor; Apoptosis; Xenograft
资金
- National Taiwan University [95R0066-BM01-02]
- Department of Health (Taiwan) [DOH96-TD-B111-001]
- National Science Council (Taiwan) [NSC96-3112-B-002-036]
Background/Aims: Hepatocelfular carcinoma (HCC) is one of the most common malignancies worldwide and novel therapies are urgently needed. Recently, aberrant expression of Aurora kinases has been reported in various human cancers including HCC. We sought to investigate the potential of a potent and selective Aurora kinase inhibitor, VE-465, for targeted therapy of HCC. Methods: Cytotoxicity effects of VE-465 were tested in Huh-7 and HepG2 cell lines. Inhibition of Aurora kinase activity was demonstrated by Western blotting and immunofluorescence staining. Mitotic perturbation was visualized by confocal microscopy. Cell cycle profiles and apoptosis were assessed by flow cytometry. In vivo efficacy was determined in nude mice with human HCC xenografts. Results: We demonstrated that VE-465 induced proliferation blockade, histone H3 (Ser10) dephosphorylation, mitotic disturbance, endoreduplication, and apoptosis in Huh-7 and HepG2 cells. We also found that VE-465 suppressed Aurora kinase activity, prevented tumor growth, and induced apoptosis in a Huh-7 xenograft model. Conclusions: These findings show that VE-465 has potent anticancer effects in human HCC. Inhibitors of Aurora kinases may deserve further exploration as molecular targeted agents against HCC. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据