Efeito do TKI-258 sobre a motilidade de células de carcinoma epidermoide oral in vitro

Abstract

Oral squamous cell carcinoma is extremely invasive, this behavior is regulated by binding of extracellular molecules to the cell membrane receptors. Currently, the blocking of these receptors with specific inhibitors is a new treatment modality of cancer. The TKI-258 inhibited phosphorylation of FGFRs VEGFRs and PDGFRs. Our aim was to analyze the effect of TKI-258 treatment on cell movement by using SCC-4 cell line from human oral squamous cell carcinoma. F-actin was stained with rhodamine conjugated to phalloidin and confocal analysis was performed. The migration and invasion (membrane covered with MatrigelTM) three-dimensional assays were performed, control and cells treated with TKI-258 that migrated through the membrane were counted after 24 hours. Control cells presented abundant cytoplasm with F-actin wide distributed and evident cell cortex, however cells treated with TKI258 at the concentrations studied showed round morphology, scanty cytoplasm, F-actin desorganized and preserved cell cortex. TKI-258 (1 μM, 5 μM and 10 μM) treatment inhibit migrating cells (ANOVA, F=97,749, df=3, 10; p<0.0001) and it was concentration dependent. Invading cell treated with 5 μM TKI-258 was significantly lower (t=6.708, df=5, p<0.001). These results suggest that the tyrosine kinase inhibitor TKI-258 has an inhibitory effect on F-actin, cell migration and cell invasion, probably these processes are regulated by FGFRs and/or PDGFRs and/or VEGFRs signaling pathways.