Cytotoxic effects of 15-deoxy-Δ12,14-prostaglandin J2 alone and in combination with dasatinib against uterine sarcoma in vitro 6

• 資料種別: 博士論文
• ISSN: 1792-0981
• タイトル: Cytotoxic effects of 15-deoxy-Δ12,14-prostaglandin J2 alone and in combination with dasatinib against uterine sarcoma in vitro
• 巻次・部編番号: 13 6
• 著者・編者: Kawakita, Takako; Nisimura, Masato; Takiguchi, Eri; Abe, Akiko; Irahara, Minoru
• 著者標目: Kawakita, Takako; Nisimura, Masato; Takiguchi, Eri; Abe, Akiko; Irahara, Minoru
• 出版事項: Spandidos publications
• 出版年月日等: 2017-04-18
• 出版年（W3CDTF）: 2017-04-18
• 並列タイトル等: 15-deoxy-Δ12,14-prostaglandin J2の単剤とダサチニブの併用療法は子宮肉腫の増殖を抑制する; CYTOTOXIC EFFECT OF 15d-PGJ2 AGAINST UTERINE SALCOMA
• タイトル（掲載誌）: Experimental and Therapeutic Medicine
• 授与機関名: 徳島大学
• 授与年月日: 2017-03-06
• 授与年月日（W3CDTF）: 2017-03-06
• 報告番号: 甲第3021号
• 学位: 博士（医学）
• 博論授与番号: 甲第3021号
• 本文の言語コード: eng
• 件名標目: 15‑deoxy‑Δ12,14‑prostaglandin J2; uterine sarcoma; dasatinib; MAPK; ERK; AKT
• 対象利用者: 一般
• 一般注記: Effective chemotherapeutic strategies for uterine sarcoma are lacking; existing therapies achieve poor response rates. Previous studies have identified the prostaglandin 15-deoxy- Δ12,14-prostaglandin J2 (15d-PGJ2) as a potential anticancer treatment; however, its effectiveness in uterine sarcoma has not been examined. Furthermore, the molecular mechanisms underlying the cytotoxic mechanism of 15d-PGJ2 remain unclear. Here, we evaluated the effects of 15d-PGJ2 alone and in combination with the tyrosine kinas inhibitor (TKI) dasatinib in uterine sarcoma cell lines (MES-SA, MES-SA/DX5 and SKN). 15d-PGJ2 inhibited cell growth and increased apoptosis. Western blotting demonstrated that 15d-PGJ2 treatment increased MEK and ERK phosphorylation, and decreased levels of phosphorylated AKT. Dasatinib in combination with 15d-PGJ2 significantly reduced cell proliferation compared with 15d-PGJ2 alone, and repressed both the AKT and MAPK pathways. The cell growth inhibition rate in the PGJ2 was 21.5±12.0, 35.3±5.4 and 28.3±4.2%, respectively (MES-SA, MES-SA/DX5 and SKN cell lines) and the cell growth inhibition rate in the combination therapy was significantly higher compared with 15d-PGJ2 alone (MES-SA; 64.2±0.8, MES-SA/DX5;23.9±8.2 and SKN; 41.4±17.6%). The PGJ2 IC50 determined by MTT assay was 27.41,10.46 and 17.38 μmol/l, respectively (MES-SA, MES-SA/DX5 and SKN cell lines) and the dasatinib IC50 was 6.68,17.30 and 6.25 μmol/l, respectively. Our findings demonstrate that 15d-PGJ2 suppresses proliferation by inactivating the AKT pathway in uterine sarcoma. Furthermore, combining 15d-PGJ2 with dasatinib produced a synergistic effect on cancer cell inhibition by repressing 15d-PGJ2-mediated activation of MAPK signaling, and further repressing AKT signaling. These results suggest that 15d-PGJ2 could be used in combination with dasatinib as a potential therapeutic approach for uterine sarcoma.
• DOI: info:doi/10.3892/etm.2017.4346; https://doi.org/info:doi/10.3892/etm.2017.4346
• 国立国会図書館永続的識別子: info:ndljp/pid/10993573; https://dl.ndl.go.jp/pid/10993573
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2017-12-04T02:02:48+09:00
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 掲載誌（URI）: https://repo.lib.tokushima-u.ac.jp/112972
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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2019-10-04 再収集