Conclusion
LEF is a potent anticancer agent with antiangiogenic effects on OSCC and might be clinically applicable to OSCC by drug repositioning.
Methods
To evaluate the inhibitory effect of LEF on OSCC, cell proliferation and wound-healing assays using human OSCC cell lines were performed. The DHODH inhibitory effect of LEF was evaluated by Western blot. To assess the suppression of pyrimidine biosynthesis induced by LEF on OSCC, cell proliferation assays with or without uridine supplementation were performed. The antiangiogenic effect of LEF was evaluated by in vitro tube formation assay using immortalized human umbilical vein endothelial cells, which were electroporatically transfected with hTERT. The tumor-suppressive effect of LEF in vivo was examined in both immunodeficient and syngeneic mice by implanting mouse OSCC cells. Tumor vascularization was evaluated by immunohistochemistry of the tumor extracted from syngeneic mice.
Results
LEF dose-dependently inhibited OSCC proliferation and migration. LEF significantly inhibited DHODH expression, and uridine supplementation rescued the inhibitory effect of LEF. LEF dose-dependently suppressed endothelial tube formation. In the animal study, LEF significantly suppressed tumor growth in both immunodeficient and syngeneic mice. Histologically, LEF decreased DHODH expression and tumor vascularization.