Human osteosarcoma cells respond to sorafenib chemotherapy by downregulation of the tumor progression factors S100A4, CXCR4 and the oncogene FOS.
Oncol Rep
; 31(3): 1147-56, 2014 Mar.
Article
en En
| MEDLINE
| ID: mdl-24378831
ABSTRACT
Osteosarcoma is a rare but aggressive bone neoplasm in humans, which is commonly treated with surgery, classical chemotherapy and radiation. Sorafenib, an inhibitor of a number of kinases targeting the Raf/MEK/ERK pathway, is a promising new chemotherapeutic agent in human medicine that has been approved since 2006 for the therapy of renal cell carcinoma and since 2007 for the treatment of hepatocellular carcinoma. Here, we studied the antimetastatic potential of 4 µM of this multikinase inhibitor in a human osteosarcoma cell line. DNA microarray-based gene expression profiling detected 297 and 232 genes upregulated or downregulated at a threshold of >2-fold expression alteration (P<0.05) in the sorafenib-treated cells. Three genes (CXCR4, FOS and S100A4) that are involved in tumor progression were chosen for validation by quantitative PCR (qPCR) and protein expression analysis. The decrease in RNA expression detected by microarray profiling was confirmed by qPCR for all three genes (P<0.01). On the protein level, sorafenib-induced reduction of S100A4 was verified both by western blotting and immunohistochemistry. For CXCR4 and c-Fos, a reduced protein expression was shown by immunohistochemistry, for c-Fos also by immunoblotting. We conclude that sorafenib could serve as a potent chemotherapeutical agent by which to inhibit the metastatic progression of osteosarcomas.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos de Fenilurea
/
Proteínas S100
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Proteínas Oncogénicas v-fos
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Niacinamida
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Receptores CXCR4
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Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Oncol Rep
Asunto de la revista:
NEOPLASIAS
Año:
2014
Tipo del documento:
Article
País de afiliación:
Austria