title: A novel multi-kinase inhibitor pazopanib suppresses growth of synovial sarcoma cells through inhibition of the PI3K-AKT pathway.
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.
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Hosaka
authors.forename: Keisuke
authors.initials: K
authors.lastname: Horiuchi
authors.forename: Masaki
authors.initials: M
authors.lastname: Yoda
authors.forename: Robert
authors.initials: R
authors.lastname: Nakayama
authors.forename: Takahide
authors.initials: T
authors.lastname: Tohmonda
authors.forename: Michiro
authors.initials: M
authors.lastname: Susa
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakamura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Chiba
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Hideo
authors.initials: H
authors.lastname: Morioka
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007191:Indazoles; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D013584:Sarcoma, Synovial / Q000188:drug therapy* / Q000201:enzymology; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D007191:Indazoles; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D011743:Pyrimidines; D020794:Receptor Protein-Tyrosine Kinases; D013449:Sulfonamides; C516667:pazopanib