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Additive antitumor effects of gefitinib and imatinib on anaplastic thyroid cancer cells

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Abstract

Purpose: Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies. Although multidisciplinary treatments have been introduced, patients with this disease rarely survive longer than 1 year. These findings prompted us to investigate the antitumor activity of molecular targeting agents in thyroid cancer cells. Methods: Two tyrosine kinase inhibitors, gefitinib and imatinib, were tested in a poorly differentiated thyroid cancer cell line, KTC-1, and two ATC cell lines, KTC-2 and KTC-3. Results: All cell lines expressed not only a target molecule of gefitinib, HER1, but also a cognate receptor, HER2. They also expressed target molecules of imatinib, c-ABL and platelet-derived growth factor receptors at various levels. Both agents had modest antitumor activity in these cell lines. Combined treatment with gefitinib and imatinib led to an additional antitumor effect. Each agent induced apoptosis and their combined treatment enhanced apoptosis associated with the down-regulation of antiapoptotic proteins, Bcl-2 and Bcl-xL. Moreover, their combined treatment additionally inhibited the growth of KTC-3 xenografts in nude mice. Conclusions: These are the first findings to suggest that both gefitinib and imatinib have antitumor activity against ATC cells and that their combined use has greater activity than either drug alone.

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Acknowledgements

This work was supported by Research Project Grants (16–501S) from Kawasaki Medical School and by a grant from the Japanese Breast Cancer Society.

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Authors and Affiliations

  1. Departments of Breast and Thyroid Surgery, Kawasaki Medical School, Kurashiki, 701-0192, Okayama, Japan

    Junichi Kurebayashi, Sumiko Okubo, Yutaka Yamamoto, Masahiko Ikeda, Katsuhiro Tanaka & Hiroshi Sonoo

  2. Department of Hygiene, Kawasaki Medical School, Kurashiki, 701-0192, Okayama, Japan

    Takemi Otsuki

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  1. Junichi Kurebayashi
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  7. Hiroshi Sonoo
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Correspondence to Junichi Kurebayashi.

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Kurebayashi, J., Okubo, S., Yamamoto, Y. et al. Additive antitumor effects of gefitinib and imatinib on anaplastic thyroid cancer cells. Cancer Chemother Pharmacol 58, 460–470 (2006). https://doi.org/10.1007/s00280-006-0185-x

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  • DOI: https://doi.org/10.1007/s00280-006-0185-x

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