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Telmisartan inhibits hepatocellular carcinoma cell proliferation in vitro by inducing cell cycle arrest
https://kagawa-u.repo.nii.ac.jp/records/299
https://kagawa-u.repo.nii.ac.jp/records/29943c6f430-427f-443c-bf62-d93dae96ee3a
| 名前 / ファイル | ライセンス | アクション |
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本文 (1.2 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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| 公開日 | 2018-05-30 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Telmisartan inhibits hepatocellular carcinoma cell proliferation in vitro by inducing 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 |
大浦, 杏子
× 大浦, 杏子
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| 抄録 | ||||||||||||
| 内容記述タイプ | Abstract | |||||||||||
| 内容記述 | Abstract Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third leading cause of cancer-related death. Telmisartan, a widely used antihypertensive drug, is an angiotensin II type 1 (AT1) receptor blocker (ARB) that might inhibit cancer cell proliferation, but the mechanisms through which telmisartan affects various cancers remain unknown. The aim of the present study was to evaluate the effects of telmisartan on human HCC and to assess the expression of microRNAs (miRNAs). We studied the effects of telmisartan on HCC cells using the HLF, HLE, HepG2, HuH-7 and PLC/PRF/5 cell lines. In our experiments, telmisartan inhibited the proliferation of HLF, HLE and HepG2 cells, which represent poorly differentiated types of HCC cells. However, HuH-7 and PLC/PRF/5 cells, which represent well-differentiated types of HCC cells, were not sensitive to telmisartan. Telmisartan induced G0/G1 cell cycle arrest of HLF cells by inhibiting the G0-to-G1 cell cycle transition. This blockade was accompanied by a marked decrease in the levels of cyclin D1, cyclin E and other cell cycle-related proteins. Notably, the activity of the AMP-activated protein kinase (AMPK) pathway was increased, and the mammalian target of rapamycin (mTOR) pathway was inhibited by telmisartan treatment. Additionally, telmisartan increased the level of caspase-cleaved cytokeratin 18 (cCK18), partially contributed to the induction of apoptosis in HLF cells and reduced the phosphorylation of ErbB3 in HLF cells. Furthermore, miRNA expression was markedly altered by telmisartan in vitro. In conclusion, telmisartan inhibits human HCC cell proliferation by inducing cell cycle arrest. |
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| 言語 | en | |||||||||||
| 学位名 | ||||||||||||
| 言語 | ja | |||||||||||
| 学位名 | 博士（医学） | |||||||||||
| 学位授与機関 | ||||||||||||
| 識別子Scheme | kakenhi | |||||||||||
| 識別子 | 16201 | |||||||||||
| 言語 | ja | |||||||||||
| 機関名 | 香川大学 | |||||||||||
| 言語 | en | |||||||||||
| 機関名 | Kagawa University | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2018-03-24 | |||||||||||
| 学位授与番号 | ||||||||||||
| 学位授与番号 | 甲第678号 | |||||||||||
| 権利 | ||||||||||||
| 言語 | en | |||||||||||
| 権利情報 | Copyright: © Oura et al. | |||||||||||
| 権利 | ||||||||||||
| 言語 | en | |||||||||||
| 権利情報Resource | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||||||||
| 権利情報 | This is an open access article distributed under the terms of Creative Commons Attribution License. | |||||||||||
| 論文ID（NAID） | ||||||||||||
| 識別子タイプ | NAID | |||||||||||
| 関連識別子 | 500001069873 | |||||||||||
| PubMed番号 | ||||||||||||
| 識別子タイプ | PMID | |||||||||||
| 関連識別子 | 29048654 | |||||||||||
| 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/10.3892/or.2017.5977 | |||||||||||
| 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/11122654 | |||||||||||
| 関連サイト | ||||||||||||
| 関連タイプ | hasVersion | |||||||||||
| 識別子タイプ | URI | |||||||||||
| 関連識別子 | http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5780034/ | |||||||||||
| 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 | hepatocellular carcinoma | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | telmisartan | |||||||||||
| 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 | angiotensin II type 1 receptor blocker | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | microRNA | |||||||||||
| KEID | ||||||||||||
| 28449 | ||||||||||||
