Background: Identification of the antitumor role of tyrosine kinase inhibitors, such as TKI-258, may
lead to novel therapeutics for Oral Squamous Cell Carcinoma (OSCC), which has high mortality rates. TKI-258
blocks Fibroblast Growth Factor Receptors (FGFRs), Platelet-Derived Growth Factor Receptors (PDGFRs), and
Endothelial Growth Factor Receptor (VEGFRs).
Objective: This study aimed to evaluate the effect of TKI-258 treatment on cell proliferation in SCC-4 cells of
Methods: BrdU and KI-67 assays were performed by using SCC-4 cells. Control was compared to 1, 5 and
10μM TKI-258 treatment. Control vehicle was compared to: 60μM LY294002 (LY), 2μM Wortmannin (WTN)
and LY+WNT. Moreover, TKI 5μM treatment was compared to: TKI 5μM+LY; TKI 5 μM+WTN; TKI
5μM+LY+WTN. After 6h of treatments, immunofluorescence stained BrdU and KI-67 positive cells. Morphometry
of proliferative cells was analyzed considering significance of p<0.05.
Results: BrdU and KI-67 assays results were similar for all experiments. TKI-258 treatment leads to an important
reduction in proliferation rate in SCC-4 cells in a concentration dependent manner. As expected, there was a
significant reduction in the percentage of proliferative cells that had PI3K inhibited. When compared with TKI 5
treatment, proliferating cells were significantly lower with simultaneous PI3K inhibition.
Conclusion: This study demonstrated that TKI-258 plays an anti-proliferative role on SCC-4 cells of OSCC. It
could be interesting to block multiples pathways such as FGFRs, PDGFRs and VEGFRs. Therefore, TKI-258 is
a promising option for novel therapeutics for OSCC, especially if associated with PI3K inhibition.