Project/Area Number |
26461175
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
|
Research Institution | Hokkaido University |
Principal Investigator |
|
Co-Investigator(Renkei-kenkyūsha) |
JINUSHI Masahisa 慶應義塾大学, 医学部, 特任准教授 (40318085)
AKITA Hirotoshi 北海道大学, 医学研究科, 教授 (70222528)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | 肺癌 / ヒストン修飾 / 癌幹細胞 / EZH2 / DZNep / HDAC / SAHA / side population / ヒストン修飾酵素 / 非小細胞肺癌 / 幹細胞 / EGFR |
Outline of Final Research Achievements |
EGFR-tyrosine kinase inhibitor (TKI) resistant non-small lung cancer (NSCLC) cell H1975 had 1% side population fraction, which showed increased tumorigenicity, elevated expression of stem cell markers and histone H3K27 trimethyl transferase EZH2, suggesting that EZH2 may play a role in maintenance of cancer stem cells. The combined treatment with inhibitors of the EZH2 and the histone deacetylases HDACs showed synergistic growth suppressive effects, suppression of EGFR signaling, and decrease in the in vivo tumor growth of H1975 cells, suggesting that the combined pharmacological targeting of the histone modification enzymes may provide more effective epigenetic therapeutics for NSCLCs including those with EGFR-TKI-resistant mutations.
|