2022 Fiscal Year Final Research Report
Elucidation of molecular mechamism of growth factor receptors downregulation by Ephedra Herb and application to molecular target drug-resistance non-small cell lung cancer
Project/Area Number |
20K07790
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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 |
Review Section |
Basic Section 52010:General internal medicine-related
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Research Institution | Kitasato University |
Principal Investigator |
Hyuga Sumiko 北里大学, 薬学部, 准教授 (60353471)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 麻黄 / c-Met / EGFR / ダウンレギュレーション / 分子標的治療薬 / 漢方薬 |
Outline of Final Research Achievements |
We have found that Ephedra Herb extract (EHE) induces downregulation of overexpressed c-Met and wild type EGFR in non-small-cell lung cancer (NSCLC) cells. Clinically, NSCLC patients who are eligible for EGFR-tyrosine kinase inhibitor (TKI) treatment are those with detected EGFR with activating mutations. Therefore, in this study, the effect of EHE on EGFR with activating mutations was investigated. EHE induced downregulation of overexpressed EGFR with activating mutations. Moreover, we examined the combined effects of EGFR-TKI, osimertinib, and EHE, because the advanced NSCLC patients are widely treated with osimertinib which binds covalently to the kinase domain of EGFR. EHE downregulated the expression of EGFR bound by osimertinib, and the combination suppressed the proliferation of NSCLC cells more effectively than did osimertinib alone. These results suggested that this combination may be effective in treating patients with advanced NSCLC with EGFR mutation.
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Free Research Field |
薬理学
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Academic Significance and Societal Importance of the Research Achievements |
学術的意義:がん細胞に過剰発現したc-Met、EGFR、及び、活性型変異EGFRをダウンレギュレーションするような分子の報告はなく、EHEの作用は新規作用であると考えられる。麻黄は細胞表面に発現する分子に作用して、細胞機能の調整を行っている可能性があり、本研究成果は漢方薬の薬効解明の糸口になると考えられる。 社会的意義:活性型変異を有するEGFR発現NSCLCには分子標的治療薬が有効であるが、c-Metを発現すれば薬剤耐性を引き起こす。EHEは活性型変異EGFRとc-Metの両方に作用することから、再発抑制に有効な併用薬となる可能性がある。
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