Development of targeted therapy to overcome drug resistance in malignant mesothelioma

2017 Fiscal Year Final Research Report

• Project/Area Number: 26461183
• 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: 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.

Free Research Field

臨床腫瘍学