2016 Fiscal Year Final Research Report
Restoration of chemoresistance by modifying epithelial-to-mesenchymal transition.
| Project/Area Number |
26461182
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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 | Chiba University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 上皮間葉移行 / TGF / FGF / EGFR / メトホルミン / ニンテダニブ / ピルフェニドン |
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| Outline of Final Research Achievements |
Epithelial-to-mesenchymal transition (EMT) is a malignant cancer phenotype. Two human lung adenocarcinoma cell lines with an EGFR mutation, PC-9 and HCC-827, were treated with TGF-b; and FGF-2 to induce EMT. A combination of TGF-beta and FGF-2 efficiently induced EMT in both cell lines: through Smad3 pathway in PC-9, and through Smad3, MEK/Erk, and mTOR pathways in HCC-827. The mTOR inhibitor PP242, metformin, and DMSO reverted EMT to different extents and through different pathways, depending on cell lines. EMT induction reduced the sensitivity to gefitinib in both cell lines and to cisplatin in HCC-827, and it increased PD-L1 expression in both cell lines. EMT reversion using each of the 3 agents partly restored chemosensitivity and suppressed PD-L1 expression. In addition, pirfenidone and nintedanib also reverted EMT. These findings suggest that EMT would be a good candidate for targeting cancer therapy.
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| Free Research Field |
腫瘍内科学
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