It has been reported that overactivation of fibroblast growth factor receptor 1 (FGFR1) is an important characteristic found in most non-small cell lung cancer (NSCLC) samples. Here, we identified a FGFR1 inhibitory peptide R1-P2 and investigated its effects on the lung cancer cells growth and angiogenesis in vitro and in vivo. Our results demonstrate that R1-P2 bound to human FGFR1 protein, and efficiently blocked the binding of FGF2 to FGFR1 in A549 and NCI-H460 cells. Moreover, this peptide significantly decreased the proliferation, migration and invasion, but promoted the apoptosis in both cell lines. In addition, R1-P2 treatment effectively inhibited the tumor growth and neovascularization in nude mice with xenografted A549 cells, and R1-P2 also significantly inhibited the FGF2-induced angiogenesis in tube formation experiment and CAM model. We further demonstrated that R1-P2 suppressed lung tumor growth through anti-angiogenic and anti-proliferative activity. Our data may provide a novle leading molecule with potential application in the treatment of FGFR1 activation related lung cancers.
Keywords: Cancer therapy; FGFR1; Lung cancer; Peptide; Phage display.