食道癌放射線耐性機序解明とHDAC阻害薬による放射線耐性克服の基礎的検討

Material type: 文書・図像類

Author: 二宮, 致ほか

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Publication date: 2016-06-10

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Note (General)：: 金沢大学附属病院光学医療診療部本研究では、食道癌における放射線耐性のメカニズムを解析し、ヒストン脱アセチル化酵素(HDAC)阻害薬であるValproic acid (VPA)の放射線耐性克服効果を基礎的に検討した。その結果、放射線照射が食道癌細胞の上皮間葉転換(EMT)と癌幹細胞様形質を誘導し、癌細...

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https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-25461909/

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Material Type: 文書・図像類
Title: 食道癌放射線耐性機序解明とHDAC阻害薬による放射線耐性克服の基礎的検討
Author/Editor: 二宮, 致
Ninomiya, Itasu
Author Heading: 二宮, 致
Ninomiya, Itasu
Publication Date: 2016-06-10
Publication Date (W3CDTF): 2016-06-10
Alternative Title: Valproic acid inhibits irradiation-induced epithelial-mesenchymal transition and stem cell-like characteristics in esophageal squamous cell carcinoma
Periodical title: 平成27(2015)年度科学研究費補助金基盤研究(C) 研究成果報告書 = 2015 Fiscal Year Final Research Report
No. or year of volume/issue: 2013-04-01 - 2016-03-31
Volume: 2013-04-01 - 2016-03-31
Pages: 5p.-
Text Language Code: jpn
Subject Heading: 食道癌
放射線治療
放射線耐性
放射線感受性
バルプロ酸
Target Audience: 一般
Note (General): 金沢大学附属病院光学医療診療部
本研究では、食道癌における放射線耐性のメカニズムを解析し、ヒストン脱アセチル化酵素(HDAC)阻害薬であるValproic acid (VPA)の放射線耐性克服効果を基礎的に検討した。その結果、放射線照射が食道癌細胞の上皮間葉転換(EMT)と癌幹細胞様形質を誘導し、癌細胞の放射線抵抗性や細胞浸潤能や遊走能が亢進した。VPAは放射線照射による食道癌のEMT変化と癌幹細胞様形質の獲得を阻止し放射線性浸潤・遊走能亢進を抑制するとともに、二重鎖切断修復酵素の阻害作用により放射線感受性を増大させ、放射線耐性克服効果を示すことが示唆された。
We investigated the mechanism of radio-resistance and the anti-radioresistant and radiosensitizing effect of classic histone deacetylase (HDAC) inhibitor valproic acid (VPA) in esophageal squamous cell carcinoma (ESCC) cells. First, we showed that 2 Gy of irradiation induced epithelial–mesenchymal transition (EMT) and cancer stem-like cell properties in ESCC TE9 cells. In addition, irradiation enhanced invasion and migration ability with upregulation of matrix metalloproteinases. Second, we found that VPA induced reversal of EMT caused by irradiation in TE9 cells, resulting in attenuated cell invasion and migration abilities. Third, VPA induced Ku70 acetylation and prolonged γH2AX levels after irradiation in three ESCC cell lines (KES, TE9, TE10). Our results suggest that VPA inhibit radiation induced EMT and show radiosensitizing effect by inhibiting DNA double strand break repair pathway in ESCC.
研究課題/領域番号:25461909, 研究期間(年度):2013-04-01 - 2016-03-31
DOI: 10.24517/00051262
Source: https://kanazawa-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=44923&item_no=1&attribute_id=26&file_no=1
https://kanazawa-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=44923&item_no=1&attribute_id=26&file_no=1
Access Restrictions: 限定公開
Rights (production): CC BY-NC-ND
Related Material: https://kaken.nii.ac.jp/search/?qm=60345618
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-25461909/
https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-25461909/25461909seika/
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 金沢大学 : 金沢大学学術情報リポジトリKURA