Epigenetic regulation shifted cellular metabolism of cancer cells, which contributed to potentiate drug sensitivity of antiangiogenic agents.

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19161
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: Chiba University
• Principal Investigator: Sato Hiromi 千葉大学, 大学院薬学研究院, 助教 (30506887)
• Research Collaborator: HISAKA Akihiro (80420206)
• Project Period (FY): 2015-04-01 – 2017-03-31
• 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

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.

Free Research Field

応用薬理学