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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

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*

Volume 20, Issue 6, 2020

Page: [751 - 755] Pages: 5

DOI: 10.2174/1871520620666200213110944

Price: $65


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 OSCC.

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.

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

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