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Apoptosis and antitumor effects induced by the combination of an mTOR inhibitor and an autophagy inhibitor in human osteosarcoma MG63 cells
https://kagawa-u.repo.nii.ac.jp/records/377
https://kagawa-u.repo.nii.ac.jp/records/37761d968a2-d90d-4b31-8a06-72e6d011e564
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
本文 (1.7 MB)
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内容の要旨 (68.8 kB)
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審査の結果の要旨 (500.9 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-07-12 | |||||
| タイトル | ||||||
| タイトル | Apoptosis and antitumor effects induced by the combination of an mTOR inhibitor and an autophagy inhibitor in human osteosarcoma MG63 cells | |||||
| 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 |
堀江, 亮佑
× 堀江, 亮佑 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Abstract The inhibition of the mammalian target of rapamycin (mTOR) signaling pathway promotes the initiation of autophagy. Although it remains under debate whether chemotherapy-induced autophagy in tumor cells is a protective response or is invoked to promote cell death, recent studies indicate that autophagy is a self-defense mechanism of cancer cells that are subjected to antitumor agents and that blocking autophagy can trigger apoptosis. The aim of this study was to examine the effects of rapamycin, an mTOR inhibitor, on MG63 osteosarcoma cells. We further examined whether the combination of rapamycin and the small molecule inhibitor of autophagy Spautin-1 (specific and potent autophagy inhibitor-1) enhanced the rapamycin-induced apoptosis in MG63 cells. We examined the effects of rapamycin treatment on cell proliferation, phosphorylation of mTOR pathway components, and autophagy by western blot analysis. Furthermore, we examined the effects of rapamycin with or without Spautin-1 on the induction of apoptosis by western blot analysis and immunohistochemical staining. We found that rapamycin inhibited cell proliferation and decreased the phosphorylation of mTOR pathway components in MG63 cells. Rapamycin induced the apoptosis of MG63 cells, and this apoptosis was enhanced by Spautin-1. It was considered that Spautin-1 suppressed the protective mechanism induced by rapamycin in tumor cells and induced apoptosis. Therefore, the combination of an mTOR inhibitor and an autophagy inhibitor may be effective in the treatment of osteosarcoma because it effectively induces the apoptotic pathway. |
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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 | ||||||
| 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 | 2016-03-24 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲第623号 | |||||
| 権利 | ||||||
| 言語 | en | |||||
| 権利情報 | Copyright: © Horie 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 | 500001356526 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 26530936 | |||||
| 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/ijo.2015.3227 | |||||
| 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/11337527 | |||||
| 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/pmc4734606/ | |||||
| 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 | autophagy | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | apoptosis | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | mTOR | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Spautin-1 | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | osteosarcoma | |||||
| KEID | ||||||
| 値 | 28741 | |||||
