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

• Material Type: 博士論文
• ISSN: 1792-0981
• Title: Cytotoxic effects of 15-deoxy-Δ12,14-prostaglandin J2 alone and in combination with dasatinib against uterine sarcoma in vitro
• Volume: 13 6
• Author/Editor: Kawakita, Takako; Nisimura, Masato; Takiguchi, Eri; Abe, Akiko; Irahara, Minoru
• Author Heading: Kawakita, Takako; Nisimura, Masato; Takiguchi, Eri; Abe, Akiko; Irahara, Minoru
• Publication, Distribution, etc.: Spandidos publications
• Publication Date: 2017-04-18
• Publication Date (W3CDTF): 2017-04-18
• Alternative Title: 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
• Periodical title: Experimental and Therapeutic Medicine
• Degree grantor/type: 徳島大学
• Date Granted: 2017-03-06
• Date Granted (W3CDTF): 2017-03-06
• Dissertation Number: 甲第3021号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3021号
• Text Language Code: eng
• Subject Heading: 15‑deoxy‑Δ12,14‑prostaglandin J2; uterine sarcoma; dasatinib; MAPK; ERK; AKT
• Target Audience: 一般
• Note (General): 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
• Persistent ID (NDL): info:ndljp/pid/10993573; https://dl.ndl.go.jp/pid/10993573
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 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
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2017-12-04T02:02:48+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): https://repo.lib.tokushima-u.ac.jp/112972
• Data Provider (Database): 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