Anti-Proliferative Role of the Tyrosine Kinase Inhibitors TKI-258 on Oral Squamous Cell Carcinoma In Vitro

Author(s):

Isadora C. Silveira, Anna Cecília D.M. Carneiro, Lorraine S. Hiss and Virgínia O. Crema*   Pages 751 - 755 ( 5 )

Abstract:

<P>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). </P><P> Objective: This study aimed to evaluate the effect of TKI-258 treatment on cell proliferation in SCC-4 cells of OSCC. </P><P> 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. </P><P> 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. </P><P> 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.</P>

Keywords:

BrdU, KI-67, PI3K, oral squamous cell carcinoma, SCC-4, tyrosine kinase inhibitors.

Affiliation:

Structural Biology Department, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, Structural Biology Department, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, Structural Biology Department, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, Structural Biology Department, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG

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