Effect of dasatinib against thyroid cancer cell lines in vitro and a xenograft model in vivo

D. Chan, Jeffrey Tyner, W. J. Chng, C. Bi, R. Okamoto, J. Said, B. D. Ngan, G. D. Braunstein, H. P. Koeffler

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Tyrosine kinase inhibitors (TKIs) have emerged as a promising class of agents against thyroid cancer. The aim of the present study was to investigate the in vitro and in vivo activity of dasatinib against a panel of thyroid cancer cell lines and explore possible mechanisms of action, using various assays and western blotting. Our results showed that dasatinib exhibits prominent cytostatic activity both in vitro and in vivo against thyroid cancer cell lines with RET/PTC rearrangement (BHP2-7) and KRAS mutation (Cal62). Although dasatinib has primarily been described as an ABL/SRCfamily kinase inhibitor, the cytostatic activity observed in the present study is mediated by several off-target effects of dasatinib, some of which have not previously been reported. These effects include a reduction in phospho-FAK, FAK, RAS, Caveolin and SYK protein levels and an increase in β-catenin protein expression, which leads to the induction of senescence, an increase in the adhesiveness of the cells, a decrease in reactive oxygen species level, and changes in the expression profile of molecules involved in cellular adhesion such as integrins. Therefore, we propose that dasatinib is an effective therapeutic agent for certain patients with thyroid cancer, and these candidate patients may be identifiable on the basis of standard genotypic analyses.

Original languageEnglish (US)
Pages (from-to)807-815
Number of pages9
JournalOncology Letters
Volume3
Issue number4
DOIs
StatePublished - Apr 2012

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Thyroid Neoplasms
Heterografts
Cell Line
Cytostatic Agents
Caveolins
Catenins
Adhesiveness
Factor IX
Proxy
Integrins
Protein-Tyrosine Kinases
Reactive Oxygen Species
Phosphotransferases
Western Blotting
Dasatinib
In Vitro Techniques
Mutation
Therapeutics

Keywords

  • Migration
  • Senescence
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Effect of dasatinib against thyroid cancer cell lines in vitro and a xenograft model in vivo. / Chan, D.; Tyner, Jeffrey; Chng, W. J.; Bi, C.; Okamoto, R.; Said, J.; Ngan, B. D.; Braunstein, G. D.; Koeffler, H. P.

In: Oncology Letters, Vol. 3, No. 4, 04.2012, p. 807-815.

Research output: Contribution to journalArticle

Chan, D, Tyner, J, Chng, WJ, Bi, C, Okamoto, R, Said, J, Ngan, BD, Braunstein, GD & Koeffler, HP 2012, 'Effect of dasatinib against thyroid cancer cell lines in vitro and a xenograft model in vivo', Oncology Letters, vol. 3, no. 4, pp. 807-815. https://doi.org/10.3892/ol.2012.579
Chan, D. ; Tyner, Jeffrey ; Chng, W. J. ; Bi, C. ; Okamoto, R. ; Said, J. ; Ngan, B. D. ; Braunstein, G. D. ; Koeffler, H. P. / Effect of dasatinib against thyroid cancer cell lines in vitro and a xenograft model in vivo. In: Oncology Letters. 2012 ; Vol. 3, No. 4. pp. 807-815.
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