Molecular mechanism for determinig the sensitivity of HDAC inhibitors in cancer cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08075
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Osaka University of Pharmaceutical Sciences (2016-2017); Nagasaki University (2015)
• Principal Investigator: Ozaki Kei-ichi 大阪薬科大学, 薬学部, 教授(移行) (50252466)
• Co-Investigator(Kenkyū-buntansha): 武田 弘資 長崎大学, 医歯薬学総合研究科(薬学系), 教授 (10313230)
• Research Collaborator: KAKIMOTO Takako 長崎大学, 医歯薬学総合研究科(薬学系), 大学院生
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: HDAC阻害剤 / ERK-MAPキナーゼ / Bim / がん分子標的

Outline of Final Research Achievements

Blockade of constitutive activation of ERK-mitogen activated protein kinase(MAPK) pathway in cancer cells increases the sensitivity of cells for new anticancer and epigenetic drug, histone deacetylase inhibitor(HDACi), however, the molecular mechanism which prescribes its sensitivity is now, unclear. In two model cells, 3T3-Raf-ER cells (normal cell model) and LK2-Raf-ER cells (cancer cell model) in which activation of ERK-MAPK pathway is induced by estradiol, proapoptotic factor Bim was very important to determine the HDACi-sensitivity in both cells. Bim could be a biomarker for determining HDACi-sensitivity. Next, we are planning to analyze the downstream kinase MNK as a new molecular target.

Free Research Field

生化学　分子生物学