Abstract
Objective: Dovitinib (TKI28) is a multitargeted tyrosine kinase inhibitor that has not been previously investigated in the pre-clinical setting for the treatment of head and neck squamous cell carcinoma (HNSCC). Dovitinib is administered orally and targets receptors (FGFR1/2/3 and PDGF-beta) known to promote cell survival and proliferation and decrease cell apoptosis.
Method: HNSCC cell lines and human tumor samples were evaluated for FGFR1/2/3, and PDGF-beta expression levels. Cell lines (FADU, SCC1, OSC19, Cal27, SCC22A) were treated with a range of physiological concentrations of dovitinib and assessed for proliferation, cytotoxicity, and apoptosis. Mice bearing HNSCC xenografts were treated with dovitinib (20 mg/kg).
Results: Elevated expression of FGFR2, FGFR3, and PDGF-beta were indentified in HNSCC cell lines and human tumor specimens. In vitro, dovitinib reduced HNSCC cell proliferation (40-80%) and viability (40-60%). In a dose-dependent fashion, dovitinib also induced cytotoxicity and apoptosis in HNSCC cell lines. When co-cultured with fibroblasts, HNSCC cells proliferation was also decreased by dovitinib. In vivo, oral administration of dovitinib resulted in significant tumor regression and growth inhibition (67%). Disease-free survival at 75 days following completion of treatment was 33% and stable disease occurred in another 33%.
Conclusion: This is the first report to demonstrate dovitinib inhibits HNSCC cell growth in vitro and in vivo.
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