Document Detail


Inhibition of Aurora kinases enhances chemosensitivity to temozolomide and causes radiosensitization in glioblastoma cells.
MedLine Citation:
PMID:  22160182     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Glioblastoma remains one of the most devastating human malignancies, and despite therapeutic advances, there are no drugs that significantly improve the patient survival. Altered expression of the Aurora kinases was found in different malignancies, and their inhibition has been studied in cancer therapy. In this study, we analyzed the expression of Aurora A and Aurora B in glioblastoma samples and also analyzed whether the effects of Aurora kinase inhibition were associated with temozolomide or not on cell lines and primary cultures of glioblastoma. MATERIALS AND METHODS: RT-PCR assays were used to determine the mRNA expression in glioblastoma tumor samples and in the cell lines. Cell proliferation was measured by XTT assay, and apoptosis was determined by flow cytometry. Drug combination analyses were made based in Chou-Talalay method. Gamma radiation for clonogenic survival used the doses of 2, 4 and 6 Gy. Changes in Aurora B level were assessed by Western blot analysis. RESULTS: Aurora A and B were expressed in glioblastoma samples as well as in the glioblastoma cell lines (n = 6). Moreover, ZM447439, a selective Aurora kinase inhibitor, decreased the proliferation separately and synergistically with temozolomide in primary cultures and cell lines of glioblastoma. ZM also enhanced the effects of radiation on the two cell lines studied (U343 and U251), mainly when associated with TMZ in U343 cells. Treatment with ZM induced apoptotic cell death and diminished Aurora B protein level. CONCLUSIONS: These data suggest that Aurora kinase inhibition may be a target for glioblastoma treatment and could be used as adjuvant to chemo- and radiotherapy.
Authors:
Kleiton Silva Borges; Angel Maurício Castro-Gamero; Daniel Antunes Moreno; Vanessa da Silva Silveira; Maria Sol Brassesco; Rosane Gomes de Paula Queiroz; Harley Francisco de Oliveira; Carlos Gilberto Carlotti; Carlos Alberto Scrideli; Luiz Gonzaga Tone
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-9
Journal Detail:
Title:  Journal of cancer research and clinical oncology     Volume:  -     ISSN:  1432-1335     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902060     Medline TA:  J Cancer Res Clin Oncol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Avenida Bandeirantes 3900, Ribeirão Preto, SP, 14048-900, Brazil, ksborges@usp.br.
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