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

• DOI: 10.1002/jor.22091
• Publication Date: 2012-02-22T14:56:01Z
• Authors: Seiichi Hosaka; Keisuke Horiuchi; Masaki Yoda; Robert Nakayama; Takahide Tohmonda; Michiro Susa; Masaya Nakamura; Kazuhiro Chiba; Yoshiaki Toyama; Hideo Morioka
• Keywords: Sulfonamides; Indazoles; G1 Phase; Receptor Protein-Tyrosine Kinases; Xenograft Model Antitumor Assays; 3. Good health; Mice; Phosphatidylinositol 3-Kinases; Sarcoma, Synovial; 03 medical and health sciences; Pyrimidines; 0302 clinical medicine; Cell Line, Tumor; Animals; Humans; Proto-Oncogene Proteins c-akt; Phosphoinositide-3 Kinase Inhibitors; Signal Transduction

AbstractSynovial 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. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1493–1498, 2012