2017 Fiscal Year Final Research Report
Development of targeted therapy to overcome drug resistance in malignant mesothelioma
Project/Area Number |
26461183
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
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Research Institution | University of Tsukuba (2015-2017) Chiba Cancer Center (Research Institute) (2014) |
Principal Investigator |
SEKINE Ikuo 筑波大学, 医学医療系, 教授 (10508310)
|
Co-Investigator(Kenkyū-buntansha) |
田川 雅敏 千葉県がんセンター(研究所), がん治療開発グループ, 部長 (20171572)
岩澤 俊一郎 千葉大学, 医学(系)研究科(研究院), その他 (00527913)
瀧口 裕一 千葉大学, 医学部附属病院, 教授 (30272321)
|
Project Period (FY) |
2014-04-01 – 2018-03-31
|
Keywords | ペメトレキセド / 薬物耐性 / CARP / AMPK / ANKRD1 |
Outline of Final Research Achievements |
We established pemetrexed (PEM)-resistant mesothelioma cells which did not show any increase of the relevant enzyme activities. We found that expression of CARP was elevated in the PEM-resistant cells with a microarray and Western blot analysis. However, down-regulation of CARP expression with si-RNA did not influence the PEM resistance.Next, we found increased phosphorylated AMPK and p70S6K levels in PEM-resistant cells, and PEM stimulation augmented these phosphorylation. An AMPK activator increased PEM resistance in the parent cells and an inhibitor decreased PEM resistance of the PEM-resistant cells. These data indicated that constitutive activation of AMPK was associated with PEM resistance.
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Free Research Field |
臨床腫瘍学
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