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

Seiichi Hosaka; Keisuke Horiuchi; Masaki Yoda; Robert Nakayama; Takahide Tohmonda; Michiro Susa; Masaya Nakamura; Kazuhiro Chiba; Yoshiaki Toyama; Hideo Morioka

doi:10.1002/jor.22091

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

Seiichi Hosaka, Keisuke Horiuchi, Masaki Yoda, Robert Nakayama, Takahide Tohmonda, Michiro Susa, Masaya Nakamura, Kazuhiro Chiba, Yoshiaki Toyama, Hideo Morioka

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1493-1498
Number of pages	6
Journal	Journal of Orthopaedic Research
Volume	30
Issue number	9
DOIs	https://doi.org/10.1002/jor.22091
Publication status	Published - 2012 Sep

Keywords

PI3K-AKT pathway
molecular targeted therapy
pazopanib
synovial sarcoma

ASJC Scopus subject areas

Orthopedics and Sports Medicine

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10.1002/jor.22091

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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.",

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AU - Hosaka, Seiichi

AU - Horiuchi, Keisuke

AU - Yoda, Masaki

AU - Nakayama, Robert

AU - Tohmonda, Takahide

AU - Susa, Michiro

AU - Nakamura, Masaya

AU - Chiba, Kazuhiro

AU - Toyama, Yoshiaki

AU - Morioka, Hideo

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AB - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

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