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Anti-diabetic drug metformin inhibits cell proliferation and tumor growth in gallbladder cancer via G0/G1 cell cycle arrest
https://kagawa-u.repo.nii.ac.jp/records/141
https://kagawa-u.repo.nii.ac.jp/records/141ce0611bf-ed2a-495d-aac4-60c8c6fe50c8
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2020-05-21 | |||||
タイトル | ||||||
タイトル | Anti-diabetic drug metformin inhibits cell proliferation and tumor growth in gallbladder cancer via G0/G1 cell cycle arrest | |||||
言語 | en | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
資源タイプ | doctoral thesis | |||||
アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
著者 |
山下, 拓磨
× 山下, 拓磨 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Gallbladder cancer is the most common biliary tract cancer with poor prognosis and wide variation in incidence rates worldwide, being very high in some countries in Latin America and Asia. Treatment of type 2 diabetes with metformin causes a reduction in the incidence of cancer. Till date, there are no reports on the anti-tumor effects of metformin in gall bladder cancer. Therefore, this study evaluated the effects of metformin on the proliferation of human gallbladder adenocarcinoma cells in vitro and in vivo, as well as explored the microRNAs associated with the anti-tumor effects of metformin. Metformin inhibited the proliferation in gallbladder adenocarcinoma cell lines NOZ, TGBC14TKB, and TGBC24TKB, and blocked the G0 to G1 transition in the cell cycle. This was accompanied by strong reduction in the expression of G1 cyclins, especially cyclin D1 and its catalytic subunits including cyclin-dependent kinase 4, and in retinoblastoma protein phosphorylation. In addition, metformin reduced the phosphorylation of receptor tyrosine kinases, especially Tie-2, ALK, PYK, EphA4, and EphA10, as well as angiogenesis-related proteins, including RANTES, TGF-β, and TIMP-1. Moreover, metformin also markedly altered microRNA expression profile leading to an anti-tumor effect. Treatment of athymic nude mice bearing xenograft tumors with metformin inhibited tumor growth. These results suggest that metformin may be used clinically for the treatment of gallbladder adenocarcinoma. | |||||
言語 | en | |||||
学位名 | ||||||
言語 | ja | |||||
学位名 | 博士(医学) | |||||
学位授与機関 | ||||||
学位授与機関識別子Scheme | kakenhi | |||||
学位授与機関識別子 | 16201 | |||||
言語 | ja | |||||
学位授与機関名 | 香川大学 | |||||
言語 | en | |||||
学位授与機関名 | Kagawa University | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2020-03-24 | |||||
学位授与番号 | ||||||
学位授与番号 | 甲第745号 | |||||
権利 | ||||||
言語 | en | |||||
権利情報 | Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. | |||||
権利 | ||||||
言語 | en | |||||
権利情報Resource | https://creativecommons.org/licenses/by-nc/4.0/ | |||||
権利情報 | This article is distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC) license. | |||||
論文ID(NAID) | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | NAID | |||||
関連識別子 | 500001458809 | |||||
PubMed番号 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 31815765 | |||||
関連サイト | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1097/CAD.0000000000000870 | |||||
関連サイト | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | URI | |||||
関連識別子 | https://dl.ndl.go.jp/pid/11679543 | |||||
他の資源との関係 | ||||||
関連名称 | This is the Accepted Version of the following article: Anti-diabetic drug metformin inhibits cell proliferation and tumor growth in gallbladder cancer via G0/G1 cell cycle arrest; Anti-cancer drugs; Volume 31 Number 3 (2020) Pages: 231-240; doi: 10.1097/CAD.0000000000000870, which has been published in final form at https://doi.org/10.1097/CAD.0000000000000870. | |||||
著者版フラグ | ||||||
出版タイプ | P | |||||
出版タイプResource | http://purl.org/coar/version/c_fa2ee174bc00049f | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | cell cycle | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | gallbladder cancer | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | metformin | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | microRNAs | |||||
KEID | ||||||
値 | 28992 |