A novel multi-kinase inhibitor pazopanib suppresses growth of synovial sarcoma cells through inhibition of the PI3K-AKT pathway

J Orthop Res. 2012 Sep;30(9):1493-8. doi: 10.1002/jor.22091. Epub 2012 Feb 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • G1 Phase / drug effects
  • Humans
  • Indazoles
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Sarcoma, Synovial / drug therapy*
  • Sarcoma, Synovial / enzymology
  • Signal Transduction / drug effects
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use*
  • Xenograft Model Antitumor Assays

Substances

  • Indazoles
  • Phosphoinositide-3 Kinase Inhibitors
  • Pyrimidines
  • Sulfonamides
  • pazopanib
  • Receptor Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-akt