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Effects of Ephedra Herb extract on the expression of EGFR-activating mutations and c-Met in non-small-cell lung cancer cell line, H1975, and its combined effects with osimertinib

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Abstract

We previously reported that the combined application of Ephedra Herb extract (EHE) and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), erlotinib, is effective in suppressing the growth of erlotinib-resistant non-small-cell lung cancer (NSCLC) cell line, H1993, xenograft tumor, and cell proliferation, and that EHE downregulates c-Met and wild-type EGFR in H1993 cells. However, it was unclear whether EHE could affect EGFR with active mutations. Clinically, advanced NSCLC patients who are eligible for EGFR-TKI treatment are those with detected EGFR with activating mutations. Therefore, it is important to clarify the effect of EHE on EGFR with activating mutations. H1975 cells express EGFR with activating mutations, L858R and T790M, and c-Met; this NSCLC cell line was used in the present study. EHE downregulated the expression of EGFR with activating mutations and c-Met, and inhibited autophosphorylation of c-Met. Proliferation of H1975 cells was suppressed by EHE in a concentration-dependent manner. These results suggest that EHE may be effective against NSCLC harboring EGFR with activating mutations. Considering the fact that advanced NSCLC patients, with an EGFR T790M mutation, are currently widely treated with the third-generation EGFR-TKI, osimertinib, we examined the combined effects of osimertinib and EHE on H1975 cells. The osimertinib and EHE combination downregulated the expression of these receptors and suppressed the proliferation of H1975 cells more effectively than did osimertinib alone, suggesting that this combination may be effective in treating patients with advanced NSCLC with the L858R + T790M EGFR mutation and c-Met.

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Data availability

Previously reported [downregulation of c-Met and EGFR in H1993 cells by EHE] was used to support this study and is available at https://doi.org/10.1155/2020/7184129. This prior study is cited at relevant places within the text as reference [22]. Previously reported [inhibition of growth of H1975 cells by EHE] was used to support this study and is available with https://doi.org/10.1007/s11418-016-0977-1. This prior study is cited at relevant places within the text as reference [24].

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Acknowledgements

This research was supported by the JPSP KAKENHI (grant numbers JP20K07790).

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Authors and Affiliations

  1. Oriental Medicine Research Center, School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato-Ku, Tokyo, 108-8642, Japan

    Eiko Mori, Sumiko Hyuga & Hiroshi Odaguchi

  2. Graduate School of Medical Sciences, Kitasato University, 1-15-1, Kitazato, Minami-Ku, Sagamihara-shi, Kanagawa, 252-0373, Japan

    Eiko Mori, Sumiko Hyuga & Katsuhiko Naoki

  3. Oriental Medicine Therapy Center, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-Ku, Tokyo, 108-8642, Japan

    Toshihiko Hanawa

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  1. Eiko Mori
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Correspondence to Sumiko Hyuga.

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Sumiko Hyuga, and Hiroshi Odaguchi received research funds from KYUSHIN PHARMACEUTICAL CO., LTD, and Tsumura Co., Ltd.

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Mori, E., Hyuga, S., Hanawa, T. et al. Effects of Ephedra Herb extract on the expression of EGFR-activating mutations and c-Met in non-small-cell lung cancer cell line, H1975, and its combined effects with osimertinib. J Nat Med 77, 523–534 (2023). https://doi.org/10.1007/s11418-023-01695-w

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