In vitro antiproliferative and antimigratory activity of dasatinib in neuroblastoma and Ewing sarcoma cell lines

  • Authors:
    • Fabio Timeus
    • Nicoletta Crescenzio
    • Abderrahim Fandi
    • Alessandra Doria
    • Luiselda Foglia
    • Luca Cordero Di Montezemolo
  • View Affiliations

  • Published online on: February 1, 2008     https://doi.org/10.3892/or.19.2.353
  • Pages: 353-359
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Abstract

Neuroblastoma (NB) and Ewing sarcoma (ES) are neuroectodermal tumors typical of pediatric age that, despite aggressive treatment, still present a poor prognosis when in advanced stages. Studies indicate that c-KIT and platelet-derived growth factor receptor (PDGFR) play a substantial role in the proliferation and survival of NB and ES cells. Dasatinib, an oral multi-targeted inhibitor of several kinases including BCR-ABL and SRC-family kinases, is also active against c-KIT and PDGFR. Here, we evaluated the effect of dasatinib on the NB cell lines SJ-N-KP, SK-N-BE, AF8 and IMR5, and on the ES lines PDE02, TC106 and 6647. Proliferation and viability assays showed that dasatinib exerts an antiproliferative activity with a peak effect occurring at 24 h. After a 24-h exposure to dasatinib at 100 nM, proliferation was inhibited by 29.4±5.7% in SJ-N-KP, 41.3±11.7% in IMR5, 35.3±7.6% in PDE02 and 14±10.6% in 6647. Dasatinib did not induce apoptosis in NB and ES cell lines. A possible antimigratory activity of dasatinib was evaluated by scratch test. Dasatinib at 100 nM inhibited the migration of NB and ES cell lines by a mean of 30.2 and 25.3%, respectively. This activity suggests a possible role of dasatinib in inhibiting metastasis and appears of particular interest, given the association between metastatic disease and poor prognosis in these tumors. In conclusion, the cytostatic and antimigratory activity of dasatinib in NB and ES cell lines and the lack of pro-apoptotic activity suggests a possible use for this compound in the treatment of these tumors as a combination with other cytotoxic therapy.

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February 2008
Volume 19 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Timeus F, Crescenzio N, Fandi A, Doria A, Foglia L and Cordero Di Montezemolo L: In vitro antiproliferative and antimigratory activity of dasatinib in neuroblastoma and Ewing sarcoma cell lines. Oncol Rep 19: 353-359, 2008
APA
Timeus, F., Crescenzio, N., Fandi, A., Doria, A., Foglia, L., & Cordero Di Montezemolo, L. (2008). In vitro antiproliferative and antimigratory activity of dasatinib in neuroblastoma and Ewing sarcoma cell lines. Oncology Reports, 19, 353-359. https://doi.org/10.3892/or.19.2.353
MLA
Timeus, F., Crescenzio, N., Fandi, A., Doria, A., Foglia, L., Cordero Di Montezemolo, L."In vitro antiproliferative and antimigratory activity of dasatinib in neuroblastoma and Ewing sarcoma cell lines". Oncology Reports 19.2 (2008): 353-359.
Chicago
Timeus, F., Crescenzio, N., Fandi, A., Doria, A., Foglia, L., Cordero Di Montezemolo, L."In vitro antiproliferative and antimigratory activity of dasatinib in neuroblastoma and Ewing sarcoma cell lines". Oncology Reports 19, no. 2 (2008): 353-359. https://doi.org/10.3892/or.19.2.353