title: Tyrosine kinase inhibitor TKI-258 inhibits cell motility in oral squamous cell carcinoma in vitro.
abstract: BACKGROUND
  Oral squamous cell carcinoma is extremely invasive, and this behavior is regulated by binding of extracellular molecules to the cell membrane receptors. The TKI-258 inhibits phosphorylation of FGFRs VEGFRs and PDGFRs. Our aim was to analyze the effect of TKI-258 treatment in cell movement using SCC-4 cell line from human oral squamous cell carcinoma.
  
  
  METHODS
  F-actin was stained with rhodamine phalloidin, and confocal analysis was performed. The migration and invasion (membrane covered with Matrigel™) three-dimensional assays were performed, and control and cells treated with TKI-258 that migrated through the membrane were counted after 24 h.
  
  
  RESULTS
  Control cells presented abundant cytoplasm with F-actin wide distributed and evident cell cortex; however, treated (1, 5 and 10 μM TKI-258) cells showed round morphology, scanty cytoplasm, F-actin disorganized and preserved cell cortex. TKI-258 (1, 5, and 10 μM) treatment inhibits migrating cells (ANOVA, F = 97.749, d.f. = 3, 10; P < 0.0001), and it was concentration dependent. Invading cell treated with 5 μM TKI-258 was significantly lower (t = 6.708, d.f. = 5, P < 0.001).
  
  
  CONCLUSIONS
  These results suggest that the tyrosine kinase inhibitor TKI-258 has an inhibitory effect on cell motility, affecting F-actin, cell migration, and cell invasion, and probably, these processes are regulated by signaling pathways FGFRs and/or PDGFRs and/or VEGFRs.
authors.affiliation: Structural Biology Department, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil.
authors.forename: Anna Cecília Dias Maciel
authors.initials: ACDM
authors.lastname: Carneiro
authors.affiliation: Structural Biology Department, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil.
authors.forename: Isadora Caixeta da
authors.initials: ICD
authors.lastname: Silveira
authors.affiliation: Structural Biology Department, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil.
authors.forename: Arthur Silva
authors.initials: AS
authors.lastname: Rezende
authors.affiliation: Structural Biology Department, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil.
authors.forename: Bruna Raphaela Oliveira
authors.initials: BRO
authors.lastname: Silva
authors.affiliation: Structural Biology Department, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil.
authors.forename: Virgínia Oliveira
authors.initials: VO
authors.lastname: Crema
mesh_terms: D000199:Actins / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D002464:Cell Migration Inhibition / Q000187:drug effects*; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D009062:Mouth Neoplasms / Q000201:enzymology / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C500007:4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; D000199:Actins; D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D015363:Quinolones; D017468:Receptors, Fibroblast Growth Factor; D042461:Vascular Endothelial Growth Factor A; D017479:Receptors, Platelet-Derived Growth Factor
keywords: TKI-258; cell invasion; cell migration; oral squamous cell carcinoma; tyrosine kinase inhibitor