Aurora kinase inhibitors synergize with paclitaxel to induce apoptosis in ovarian cancer cells

Show simple item record Scharer, Christopher D. en_US Laycock, Noelani en_US Osunkoya, Adeboye O. en_US Logani, Sanjay en_US McDonald, John F. en_US Benigno, Benedict B. en_US Moreno, Carlos S. en_US 2010-04-21T14:03:59Z 2010-04-21T14:03:59Z 2008-12-11
dc.identifier.citation Christopher D. Scharer, Noelani Laycock, Adeboye O. Osunkoya, Sanjay Logani, John F. McDonald, Benedict B. Benigno, and Carlos S. Moreno, "Aurora kinase inhibitors synergize with paclitaxel to induce apoptosis in ovarian cancer cells," Journal of Translational Medicine 2008, 6:79. en_US
dc.identifier.issn 1479-5876
dc.description © 2008 Scharer et al; licensee BioMed Central Ltd. The electronic version of this article is the complete one and can be found online at: en_US
dc.description DOI:10.1186/1479-5876-6-79
dc.description.abstract Background: A large percentage of patients with recurrent ovarian cancer develop resistance to the taxane class of chemotherapeutics. While mechanisms of resistance are being discovered, novel treatment options and a better understanding of disease resistance are sorely needed. The mitotic kinase Aurora-A directly regulates cellular processes targeted by the taxanes and is overexpressed in several malignancies, including ovarian cancer. Recent data has shown that overexpression of Aurora-A can confer resistance to the taxane paclitaxel. Methods: We used expression profiling of ovarian tumor samples to determine the most significantly overexpressed genes. In this study we sought to determine if chemical inhibition of the Aurora kinase family using VE-465 could synergize with paclitaxel to induce apoptosis in paclitaxel-resistant and sensitive ovarian cancer cells. Results: Aurora-A kinase and TPX2, an activator of Aurora-A, are two of the most significantly overexpressed genes in ovarian carcinomas. We show that inhibition of the Aurora kinases prevents phosphorylation of a mitotic marker and demonstrate a dose-dependent increase of apoptosis in treated ovarian cancer cells. We demonstrate at low doses that are specific to Aurora-A, VE-465 synergizes with paclitaxel to induce 4.5-fold greater apoptosis than paclitaxel alone in 1A9 cells. Higher doses are needed to induce apoptosis in paclitaxel-resistant PTX10 cells. Conclusion: Our results show that VE-465 is a potent killer of taxane resistant ovarian cancer cells and can synergize with paclitaxel at low doses. These data suggest patients whose tumors exhibit high Aurora-A expression may benefit from a combination therapy of taxanes and Aurora-A inhibition. en_US
dc.language.iso en_US en_US
dc.publisher Georgia Institute of Technology en_US
dc.subject Aurora-A inhibition en_US
dc.subject Chemotherapeutics en_US
dc.subject Taxane resistant ovarian cancer cells en_US
dc.subject VE-465 en_US
dc.subject Recurrent ovarian cancer en_US
dc.title Aurora kinase inhibitors synergize with paclitaxel to induce apoptosis in ovarian cancer cells en_US
dc.type Article en_US
dc.contributor.corporatename Georgia Institute of Technology. School of Biology en_US
dc.contributor.corporatename Emory University. Dept. of Pathology and Laboratory Medicine en_US
dc.contributor.corporatename Emory University. Program in Genetics and Molecular Biology en_US
dc.contributor.corporatename Georgia Institute of Technology. Ovarian Cancer Institute en_US
dc.contributor.corporatename Winship Cancer Institute of Emory University en_US
dc.publisher.original BioMed Central
dc.identifier.doi 10.1186/1479-5876-6-79

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