title: Additive antitumor effects of gefitinib and imatinib on anaplastic thyroid cancer cells.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Breast and Thyroid Surgery, Kawasaki Medical School, Kurashiki, 701-0192, Okayama, Japan. kure@med.kawasaki-m.ac.jp
authors.forename: Junichi
authors.initials: J
authors.lastname: Kurebayashi
authors.forename: Sumiko
authors.initials: S
authors.lastname: Okubo
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ikeda
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Takemi
authors.initials: T
authors.lastname: Otsuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sonoo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D004357:Drug Synergism; D005260:Female; D000077156:Gefitinib; D006801:Humans; D000068877:Imatinib Mesylate; D051379:Mice; D010879:Piperazines / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D017931:DNA Primers; D010879:Piperazines; D011743:Pyrimidines; D011799:Quinazolines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib