Abstract:
Sunitinib malate is a small molecule that targets multiple receptor tyrosine kinases and blocks their activity. Receptors targeted by sunitinib
are implicated in tumor vascularization and are overexpressed by vascular tumors encountered in infants, namely, hemangiomas. Of note
is that there is still no definitive treatment for these commonly occurring tumors of infancy. The purpose of this study was to investigate
the effects of sunitinib malate on hemangioma using endothelial cells isolated from a murine model of the neoplasm (sEnd.2). The effects
of the drug on cell growth were evaluated using the crystal violet assay and flow cytometry, while the scratch assay was employed to
measure cell migration. Proteins associated with cell migration and angiogenesis were detected using western blotting. Sunitinib was
investigated further to determine its effects on the production of reactive oxygen species, a parameter associated with the promotion
of neovascularization in tumors. The results showed that sunitinib significantly reduced the growth of sEnd.2 cells by causing the cells
to accumulate in the sub-G1 phase of the cell cycle, and also induced a significant decrease in the migration of these hemangioma cells
(P < 0.05). The western blot assay showed a decrease in the expression of adhesion proteins, focal adhesion kinase and paxillin at IC50
doses, although the expression of cadherin did not change significantly (P < 0.05). In addition, transforming growth factor-β1 (TGF-β1)
expression was decreased in sunitinib-treated cells at the same dose. The adhesion proteins as well as TGF-β1 regulate cell movement and
have been implicated in tumor progression. Thus, sunitinib malate may have potential in the treatment of hemangiomas.
