Valproic acid inhibits irradiation-induced epithelial-mesenchymal transition and stem cell-like characteristics in esophageal squamous cell carcinoma
| Project/Area Number |
25461909
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
藤村 隆 金沢大学, 医学系, 准教授 (50262580)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 食道癌 / 放射線治療 / 放射線耐性 / 放射線感受性 / バルプロ酸 / ヒストン脱アセチル化阻害剤 / 上皮間葉転換 / 放射線 / 上皮間葉移行 / HDAC阻害剤 / 放射線照射 / がん幹細胞 |
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| Outline of Final Research Achievements |
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.
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Report
(4 results)
Research Products
(4 results)
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[Journal Article] Inhibitory effects of valproic acid in DNA double-strand break repair after irradiation in esophageal squamous carcinoma cells.2015
Author(s)
Makita N, Ninomiya I, Tsukada T, Okamoto K, Harada S, Nakanuma S, Sakai S, Makino I, Kinoshita J, Hayashi H, Oyama K, Nakagawara H, Miyashita T, Tajima H, Takamura H, Fushida S, Ohta T
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Journal Title
Oncol Rep.
Volume: 34(3)
Issue: 3
Pages: 1185-1192
DOI
Related Report
Peer Reviewed / Open Access
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