Authors: Kleiton Silva Borges Angel Maurício CastroGamero 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
Publish Date: 2011/12/09
Volume: 138, Issue: 3, Pages: 405-414
Abstract
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 glioblastomaRTPCR 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 ChouTalalay 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 analysisAurora 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 levelWe would like to thank Patrícia Vianna Bonini Palma Camila Cristina de Oliveira Menezes Bonaldo and Daiane Fernanda dos Santos HemocentroFMRPUSP Ribeirão Preto Brazil for their assistance with the flow cytometry Financial Support from Fundação de Amparo a Pesquisa do Estado de São Paulo FAPESP process number 2009/501182 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior and Fundação de Apoio ao Ensino Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo is acknowledged
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