| Project/Area Number |
15K19161
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied pharmacology
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| Research Institution | Chiba University |
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Principal Investigator |
Sato Hiromi 千葉大学, 大学院薬学研究院, 助教 (30506887)
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| Research Collaborator |
HISAKA Akihiro (80420206)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 細胞内代謝 / エピジェネティック調節 / 薬物耐性 / 腎細胞がん / ヒストン脱アセチル化酵素阻害薬 / チロシンキナーゼ阻害薬 / 酸化的リン酸化 / エピジェネティクス / トリコスタチンA / スニチニブ / 薬物感受性 / 血管新生阻害薬 / HDAC阻害薬 / 代謝 / CE-TOFMS / メタボローム |
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| Outline of Final Research Achievements |
Recently, drug resistance of cancer cells is drawn attention to its specific anaerobic metabolism. In this study, we investigated whether trichostain A (TSA), a histone deacetylase inhibitor, can remedy biased metabolism of renal cell carcinoma (RCC) by epigenetic regulation. Moreover, we elucidated that if such a metabolic shift contributes to sensitize drug resistance against sunitinib (SU), a first-line drug for RCC. Hydrophilic metabolites were extracted from TSA treated human RCC cells (786-O) and analyzed by capillary electrophoresis mass spectrometry (CE-MS), while mRNA expressions were analyzed by DNA microarray. As a result, it was suggested that TSA increased oxidative phosphorylation of 786-O while production of amino acids and nucleic acids were suppressed. A complex one inhibitor, metformin reversed the cytotoxic effect of SU and TSA combination. Taken together, epigenetic agents have a possibility to treat cancer cells via modification of cancer cell metabolism.
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