| 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 |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | University of Tsukuba (2015-2017)
Chiba Cancer Center (Research Institute) (2014) |
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Principal Investigator |
SEKINE Ikuo 筑波大学, 医学医療系, 教授 (10508310)
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| 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)
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| 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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ペメトレキセド / 薬物耐性 / CARP / AMPK / ANKRD1 / 悪性中皮腫 / 耐性 / 薬剤耐性 / 増殖因子 / インシュリン様増殖因子 / 化学療法 / 遺伝子発現 |
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| 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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