Cancer Chemotherapy and Pharmacology

, Volume 58, Issue 4, pp 460–470

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

  • Junichi Kurebayashi
  • Sumiko Okubo
  • Yutaka Yamamoto
  • Masahiko Ikeda
  • Katsuhiro Tanaka
  • Takemi Otsuki
  • Hiroshi Sonoo
Original Article

DOI: 10.1007/s00280-006-0185-x

Cite this article as:
Kurebayashi, J., Okubo, S., Yamamoto, Y. et al. Cancer Chemother Pharmacol (2006) 58: 460. doi:10.1007/s00280-006-0185-x

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.

Keywords

Anaplastic thyroid cancer Apoptosis Bcl-2 Bcl-xL Gefitinib Imatinib 

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Junichi Kurebayashi
    • 1
  • Sumiko Okubo
    • 1
  • Yutaka Yamamoto
    • 1
  • Masahiko Ikeda
    • 1
  • Katsuhiro Tanaka
    • 1
  • Takemi Otsuki
    • 2
  • Hiroshi Sonoo
    • 1
  1. 1.Departments of Breast and Thyroid SurgeryKawasaki Medical SchoolOkayamaJapan
  2. 2.Department of HygieneKawasaki Medical SchoolOkayamaJapan