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2014 Fiscal Year Final Research Report

Inhibition of inducing multidrug resistance in human osteosarcoma cells by histone deacetylase inhibitor and DNA methylation inhibitor

Research Project

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Project/Area Number 24592247
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionHyogo Medical University

Principal Investigator

TERADA NOBUYUKI  兵庫医科大学, 医学部, 名誉教授 (50150339)

Co-Investigator(Kenkyū-buntansha) NAKASHO Keiji  兵庫医科大学, 医学部, 教授 (00217712)
YAMANEGI Koji  兵庫医科大学, 医学部, 講師 (00434944)
YAMADA Naoko  兵庫医科大学, 医学部, 講師 (10319858)
HATA Masaki  兵庫医科大学, 医学部, 研究生(研究員) (10446057)
OHYAMA Hideki  兵庫医科大学, 医学部, 非常勤講師 (90280685)
Project Period (FY) 2012-04-01 – 2015-03-31
Keywords骨肉腫 / 薬剤耐性 / 非ステロイド系抗炎症剤
Outline of Final Research Achievements

We investigated that the combination of histone deacetylase (HDAC) inhibitor, hydralazine (DNA methylation inhibitor) and celecoxib (nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitor) inhibit inducing the expression of multidrug resistance (MDR) protein (MDR-1, MRP-1) in osteosarcoma cells without inhibiting cytotoxic sensitivity. The combination of HDAC inhibitor and celecoxib significantly inhibits cell-proliferation. This combination showed different reactions depending on the type of cells but generally inhibited. HDAC inhibitor alone increased MDR activity, however, combined with celecoxib reduced the activity depended on MDR-1 and MRP-1. These results suggest that combined treatment of HDAC inhibitor, hydralazine and celecoxib may be a useful for enhancing the effect of chemotherapy for osteosarcoma.

Free Research Field

実験病理学

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Published: 2016-06-03  

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