Therapeutic potential of the antidiabetic drug metformin in small bowel adenocarcinoma

• Material Type: 博士論文
• Title: Therapeutic potential of the antidiabetic drug metformin in small bowel adenocarcinoma
• Author/Editor: 千代, 大翔
• Author Heading: 千代, 大翔
• Publication Date: 2018-03-24
• Publication Date (W3CDTF): 2018-03-24
• Degree grantor/type: 香川大学
• Date Granted: 2018-03-24
• Date Granted (W3CDTF): 2018-03-24
• Dissertation Number: 甲第682号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第682号
• Text Language Code: eng
• Alias of Author: Chiyo, Taiga
• Subject Heading: small bowel adenocarcinoma; metformin; cell cycle; microRNAs; cyclin D1; AMPKα
• Target Audience: 一般
• Note (General): AbstractSmall bowel adenocarcinoma (SBAC) accounts for 3% of all gastrointestinal tract tumors and approximately 0.5% of all cancer cases. Recent studies have indicated that the use of metformin, one of the most commonly prescribed antidiabetic drugs, is associated with a better prognosis for certain malignant diseases. However, there have been no reports on the effect of metformin in SBAC. In the present study, we evaluated the effect of metformin on human SBAC cell proliferation in vitro and in vivo and identified the microRNAs (miRNAs) associated with its antitumor effects. Metformin inhibited the proliferation of HuTu80 cells in a time- and dose-dependent manner. Importantly, metformin reduced the expression of cyclin D1, cyclin E, cyclin-dependent kinase 4, and phosphorylated retinoblastoma protein, which resulted in cell cycle arrest at the G0/G1 phase. This arrest was accompanied by activation of AMPKα and inhibition of mammalian target of rapamycin and p70s6k. Additionally, metformin reduced the levels of phosphorylated epidermal growth factor receptor and ROR2 as well as markedly altered miRNA expression in HuTu80 cells. Metformin also inhibited tumor growth in vivo in a xenograft mouse model. Our data suggest that metformin might have therapeutic potential in SBAC.
• DOI: info:doi/10.3892/ijo.2017.3971; https://doi.org/info:doi/10.3892/ijo.2017.3971
• Persistent ID (NDL): info:ndljp/pid/11122665; https://dl.ndl.go.jp/pid/11122665
• 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): 2018-08-03T23:36:01+09:00
• Date Created (W3CDTF): 2020-10-27
• Format (IMT): 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://kagawa-u.repo.nii.ac.jp/records/303
• 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