Wnt/β-catenin経路を介した分子標的治療の開発と抗腫瘍メカニズムの解明

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Author: 山本, 憲男ほか

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Publication date: 2020-05-21

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Note (General)：: 金沢大学医薬保健学総合研究科本研究では，軟部肉腫の主要病型である滑膜肉腫と線維肉腫に対するGSK3β阻害剤の治療効果と作用機序を検討した．本研究により，滑膜肉腫と線維肉腫において，CDK-cyclin複合体を介した細胞周期の進行による生存・増殖と，MMP-2を介した浸潤が，GSK3βに依存することが...

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Material Type: 文書・図像類
Title: Wnt/β-catenin経路を介した分子標的治療の開発と抗腫瘍メカニズムの解明
Author/Editor: 山本, 憲男
Yamamoto, Norio
Author Heading: 山本, 憲男
Yamamoto, Norio
Publication Date: 2020-05-21
Publication Date (W3CDTF): 2020-05-21
Alternative Title: Glycogen synthase kinase 3beta as a potential therapeutic target in synovial sarcoma and fibrosarcoma
Periodical title: 令和1(2019)年度科学研究費補助金基盤研究(C) 研究成果報告書 = 2019 Fiscal Year Final Research Report
No. or year of volume/issue: 2016-04-01 - 2020-03-31
Volume: 2016-04-01 - 2020-03-31
Pages: 4p.-
Text Language Code: jpn
Subject Heading: GSK3β
軟部肉腫
分子標的治療
Orthopaedic surgery
Target Audience: 一般
Note (General): 金沢大学医薬保健学総合研究科
本研究では，軟部肉腫の主要病型である滑膜肉腫と線維肉腫に対するGSK3β阻害剤の治療効果と作用機序を検討した．本研究により，滑膜肉腫と線維肉腫において，CDK-cyclin複合体を介した細胞周期の進行による生存・増殖と，MMP-2を介した浸潤が，GSK3βに依存することが示唆された．リチウムやシメチジンなど，躁うつ病や胃潰瘍など臨床で広く使用され，安全性の確認されている薬剤がGSK3β活性阻害作用を有することが知られており，滑膜肉腫や線維肉腫においても早期の臨床応用が期待できることを明らかとした．
We investigated the expression, activity and putative pathological role of GSK3β in synovial sarcoma and fibrosarcoma, comprising the majority of STS that are encountered in orthopedics. Expression of the active form of GSK3β was higher in synovial sarcoma and in fibrosarcoma (HT1080) tumor cell lines than in untransformed fibroblast (NHDF) cells that are assumed to be the normal mesenchymal counterpart cells. Inhibition of GSK3β activity by pharmacological agents or of its expression by RNA interference suppressed the proliferation of sarcoma cells and their invasion of collagen gel, as well as inducing their apoptosis. These effects were associated with G0/G1-phase cell cycle arrest and decreased expression of cyclin D1, CDK4 and MMP2. Intraperitoneal injection of the GSK3β inhibitors attenuated the growth of SYO-1 and HT1080 xenografts in athymic mice without obvious detrimental effects. It also mitigated cell proliferation and induced apoptosis in the tumors of mice.
研究課題/領域番号:16K10850, 研究期間(年度):2016-04-01 - 2020-03-31
出典：「Wnt/β-catenin経路を介した分子標的治療の開発と抗腫瘍メカニズムの解明」研究成果報告書　課題番号16K10850（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-16K10850/16K10850seika/)を加工して作成
DOI: 10.24517/00057396
Access Restrictions: 限定公開
Related Material: https://kaken.nii.ac.jp/search/?qm=90332668
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16K10850/
https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-16K10850/16K10850seika/
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 金沢大学 : 金沢大学学術情報リポジトリKURA