BACKGROUND: Dovitinib is a receptor tyrosine kinase (RTK) inhibitor targeting 
vascular endothelial growth factor receptors, fibroblast growth factor receptors 
and platelet-derived growth factor receptor β. Dovitinib is currently in 
clinical trials for the treatment of hepatocellular carcinoma (HCC).
METHOD: In this study, we used five HCC cell lines and five endothelial cell 
lines to validate molecular and cellular targets of dovitinib.
RESULTS: Tumor growth and pulmonary metastasis were significantly suppressed in 
an orthotopic HCC model. Immunoblotting revealed that among known dovitinib 
targets, only PDGFR-β was expressed in two HCC cell lines, while four of five 
endothelial lines expressed PDGFR-β, FGFR-1, and VEGFR-2. Dovitinib inhibited 
endothelial cell proliferation and motility at 0.04 μmol/L, a pharmacologically 
relevant concentration; it was unable to inhibit the proliferation or motility 
of HCC cells at the same concentration. Immunohistochemical analyses showed that 
dovitinib significantly decreased the microvessel density of xenograft tumors, 
inhibiting proliferation and inducing apoptosis in HCC cells.
CONCLUSION: Our findings indicate that dovitinib inhibits HCC growth and 
metastasis preferentially through an antiangiogenic mechanism, not through 
direct targeting of HCC cells.