Tyrosine kinase inhibitor TKI-258 inhibits cell motility in oral squamous cell carcinoma in vitro

BackgroundOral 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. MethodsF-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. ResultsControl cells presented abundant cytoplasm with F-actin wide distributed and evident cell cortex; however, treated (1, 5 and 10 M TKI-258) cells showed round morphology, scanty cytoplasm, F-actin disorganized and preserved cell cortex. TKI-258 (1, 5, and 10 M) 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 M TKI-258 was significantly lower (t = 6.708, d.f. = 5, P < 0.001). ConclusionsThese 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.