Investigation on anticancer drugs-induced epithelial-mesenchymal transition for development of preventive approach to drug-induced lung injury
| Project/Area Number |
19K16447
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Hiroshima University |
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Principal Investigator |
Kawami Masashi 広島大学, 医系科学研究科(薬), 助教 (20725775)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | 薬剤性肺障害 / 上皮間葉転換 / セルソーティング / バイオインフォマティクス / 抗がん剤 / メトトレキサート / p53 / 肺胞上皮 |
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| Outline of Research at the Start |
本研究では、まず抗がん剤によってEMTが誘発される細胞と誘発されない細胞の分取およびそれらの安定的な維持培養法の確立を試みる。その後、それら細胞の分子生物学的プロファイルの比較検討を通じて、EMTが誘発される細胞にのみに認められる特徴的な因子を、バイオインフォマティクスの手法を用いて特定する。特定した候補因子のノックダウンや過剰発現系を用いて、薬剤誘発性EMTや抗がん効果におけるそれら因子の寄与について検証し、最終的に薬剤誘発性EMTに特異的な因子の特定を目指す。
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| Outline of Final Research Achievements |
Chemotherapeutic drugs often induces serious lung diseases as a adverse drug reaction, which is triggered by epithelial-mesenchymal transition (EMT) in injured alveolar epithelial cells. However, few mechanistic studies focusing on the drug-induced EMT is performed. The present study aimed to clarify the molecules specifically involved in anticancer drug-induced EMT.
In this study, several factors such as Nrf2, ITGA2, and p53 were closely associated with EMT induced by methotrexate (MTX), a popular chemotherapeutic agent. In particular, p53 contributed to MTX-induced EMT, but not antitumor effects, which would provide a perspective that p53 may be a one of specific molecules specifically associated with MTX-induced EMT.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で得られた知見は、これまで不明であった薬物誘発性上皮間葉転換機構の一端を解明したものであり、肺線維症をはじめとした上皮間葉転換に関連する副作用の発症を予防しながら抗がん剤治療の継続が望める画期的な治療法の構築に資する有用な基礎的知見になると考えられる。
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Report
(4 results)
Research Products
(25 results)
