| Purpose In this paper, we attempt to evaluate the therapeutic potential of bFGF antagonistic peptide(named as P7) using as a potent bFGF antagonist via exploration of its antitumor effect on NSCLC.Methods Cell viability was measured by CCK-8. Cell cycle progression was determined by propidiumiodide staining and flow cytometry. Changes in Erk1/2, P38, Akt, and STAT3phosphorylation andCyclin D1expression were detected by Western blotting. ELISA, Western blotting and RT-qPCR wereapplied to detect the expression of angiogenesis-associated proteins. Nuclear and cytoplasmic proteinextraction combined with Western blotting was carried out to investigate the influence of P7on bFGFinternalization. Two Dimensional Gel Electrophoresis combined with tandem time-of-flight massspectrometry analysis was performed to investigate the influence of P7on the protein profiles ofNSCLC. The expression levels of differentially expressed proteins identified by proteomic approachwere confirmed by RT-qPCR.Results P7peptides inhibited bFGF-stimulated proliferation of NSCLC cell lines including A549，H460, and H1299. The inhibitory mechanisms of P7involved cell cycle arrest at the G0/G1phasecaused by suppression of Cyclin D1, blockade of the activationsof Erk1/2, P38, Akt and STAT3, andinhibition of bFGF internalization. Moreover, P7not only inhibited the expressions of angiogenesisrelated factors including VEGF, MMP-2and MMP-9at both transcriptional and translational levels,but also induced significant changes in the expression levels of proteins related to tumor growth andprogress.Conclusions bFGF antagonistic peptides with potent anti-proliferation and anti-angiogenesis propertiesmay have therapeutic potential in NSCLC. |
