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Gewählte Publikation:

Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2014

AutorInnen: Walter, I; Wolfesberger, B; Miller, I; Mair, G; Burger, S; Gallè, B; Steinborn, R

Titel: Human osteosarcoma cells respond to sorafenib chemotherapy by downregulation of the tumor progression factors S100A4, CXCR4 and the oncogene FOS.

Quelle: Oncol Rep. 2014; 31(3):1147-1156



Autor/innen der Vetmeduni Vienna:

Burger Stefanie
Mair Georg
Miller Ingrid
Steinborn Ralf
Walter Ingrid
Wolfesberger Birgitt

Beteiligte Vetmed-Organisationseinheiten
Institut für Medizinische Biochemie
Institut für Topographische Anatomie
Universitätsklinik für Kleintiere, Klinische Abteilung für Interne Medizin Kleintiere
Tropenveterinärmedizin
VetCore


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.

Keywords Pubmed: Antineoplastic Agents/pharmacology*
Bone Neoplasms
Cell Line, Tumor
Down-Regulation
Drug Screening Assays, Antitumor
Gene Expression Regulation, Neoplastic/drug effects
Humans
Niacinamide/analogs & derivatives*
Niacinamide/pharmacology
Oligonucleotide Array Sequence Analysis
Oncogene Proteins v-fos/genetics
Oncogene Proteins v-fos/metabolism*
Osteosarcoma
Phenylurea Compounds/pharmacology*
Receptors, CXCR4/genetics
Receptors, CXCR4/metabolism*
S100 Proteins/genetics
S100 Proteins/metabolism*
Transcriptome/drug effects


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