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Hsp90 inhibitor induces autophagy and apoptosis in osteosarcoma cells
https://kagawa-u.repo.nii.ac.jp/records/233
https://kagawa-u.repo.nii.ac.jp/records/2338c28619d-8455-4b3b-a94a-4f33b85ae6cc
| 名前 / ファイル | ライセンス | アクション |
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本文 (1.8 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||||
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| 公開日 | 2019-08-01 | |||||||||||||
| タイトル | ||||||||||||||
| タイトル | Hsp90 inhibitor induces autophagy and apoptosis in osteosarcoma 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 |
森, 正樹
× 森, 正樹
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| 抄録 | ||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||
| 内容記述 | Abstract Heat shock protein 90 (Hsp90) is constitutively expressed at 2‑10‑fold higher levels in tumor cells compared to normal cells, suggesting that it may be critically important for tumor cell growth and survival. These features make Hsp90 a potential target for anticancer drug development. Inhibition of Hsp90 activity not only results in rapid degradation of Hsp90 client proteins but also induces apoptosis of various tumor cells. Hsp90 also plays an important role in autophagy. An Hsp90 inhibitor induces autophagy through inhibition of mTOR. It is still under debate whether chemotherapy‑induced autophagy in tumor cells is a protective response or is invoked to promote cell death. The aim of this study was to examine the effects of the Hsp90 inhibitor, geldanamycin (GA), on KTHOS osteosarcoma cells. We further examined whether a combination of GA and the autophagy inhibitor 3‑methyladenine (3‑MA) enhanced GA‑induced apoptosis in KTHOS cells. GA had an inhibitory effect on cell proliferation and inhibited the Akt/mTOR signaling pathway in KTHOS cells. GA alone induced autophagy and apoptosis in KTHOS cells, but treatment with a combination of GA and 3‑MA suppressed autophagy and induced apoptosis to a much greater extent than GA alone in these cells. It was considered that the autophagy inhibitor 3‑MA suppressed a protective mechanism induced by Hsp90 inhibitor in tumor cells and induced apoptosis. Therefore, the combination of an Hsp90 inhibitor and an autophagy inhibitor may be an effective treatment for osteosarcoma because this combination effectively induces apoptotic pathways. |
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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 | 2015-03-24 | |||||||||||||
| 学位授与番号 | ||||||||||||||
| 学位授与番号 | 甲第601号 | |||||||||||||
| 権利 | ||||||||||||||
| 言語 | en | |||||||||||||
| 権利情報 | Copyright: © Mori et al. | |||||||||||||
| 権利 | ||||||||||||||
| 言語 | en | |||||||||||||
| 権利情報Resource | https://creativecommons.org/licenses/by-nc/3.0/ | |||||||||||||
| 権利情報 | This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0]. | |||||||||||||
| 論文ID（NAID） | ||||||||||||||
| 識別子タイプ | NAID | |||||||||||||
| 関連識別子 | 500001358769 | |||||||||||||
| PubMed番号 | ||||||||||||||
| 識別子タイプ | PMID | |||||||||||||
| 関連識別子 | 25351442 | |||||||||||||
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| 関連タイプ | isVersionOf | |||||||||||||
| 識別子タイプ | DOI | |||||||||||||
| 関連識別子 | https://doi.org/10.3892/ijo.2014.2727 | |||||||||||||
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| 関連タイプ | isIdenticalTo | |||||||||||||
| 識別子タイプ | URI | |||||||||||||
| 関連識別子 | https://dl.ndl.go.jp/pid/11344366 | |||||||||||||
| 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/pmc4238730/ | |||||||||||||
| 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 | |||||||||||||
| KEID | ||||||||||||||
| 27640 | ||||||||||||||
