Abstract
Synovial sarcoma is an aggressive soft tissue sarcoma with only a modest response to conventional cytotoxic agents. In the present study, we evaluated the potential antitumor effects of a novel anti-angiogenesis agent, pazopanib, against synovial sarcoma cells. We found that pazopanib directly inhibited the growth of synovial sarcoma cells by inducing G1 arrest. Multiplex analyses revealed that the PI3K-AKT pathway was highly suppressed in pazopanib-sensitive synovial sarcoma cells. Furthermore, administration of pazopanib highly suppressed the tumor growth in a xenograft model. Taken together, these results suggest pazopanib as a possible agent against synovial sarcoma and may warrant further clinical studies.
Copyright © 2012 Orthopaedic Research Society.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line, Tumor
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G1 Phase / drug effects
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Humans
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Indazoles
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Mice
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / metabolism
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Pyrimidines / pharmacology
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Pyrimidines / therapeutic use*
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Receptor Protein-Tyrosine Kinases / metabolism
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Sarcoma, Synovial / drug therapy*
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Sarcoma, Synovial / enzymology
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Signal Transduction / drug effects
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Sulfonamides / pharmacology
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Sulfonamides / therapeutic use*
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Xenograft Model Antitumor Assays
Substances
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Indazoles
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Phosphoinositide-3 Kinase Inhibitors
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Pyrimidines
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Sulfonamides
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pazopanib
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Receptor Protein-Tyrosine Kinases
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Proto-Oncogene Proteins c-akt