Antitumor Activity of Lenvatinib (E7080): An Angiogenesis Inhibitor That Targets Multiple Receptor Tyrosine Kinases in Preclinical Human Thyroid Cancer Models
Figure 3
Effect of the selective FGFR kinase inhibitor PD173074 on the FGFR signaling pathway in human DTC RO82-W-1 cells. (a) Western blot analysis of the expression of FGF receptors in vitro. Expression levels of FGF receptors in RO82-W-1 cells were compared to those in Nthy-ori 3-1 cells (normal thyroid cells). (b) Western blot analysis of the effects of PD173074 on the phosphorylation of FGFR1 and its downstream effectors. After starvation overnight, RO82-W-1 cells were treated with PD173074 at the indicated concentrations for 1 h and were then stimulated for 10 min with bFGF (20 ng/mL) and heparin before being lysed. (c) Antitumor activity of PD173074 against RO82-W-1 xenografts in nude mice. Nude mice bearing RO82-W-1 xenografts were treated orally once daily for 14 days with either vehicle or PD173074 at the indicated doses when tumor volumes reached about 300 mm3 (day 1). The tumor volume was measured on the indicated days after administrations. Each group consisted of 5 mice. Data are shown as means ± SD. compared with vehicle-treated mice.
