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Fibroblast growth factor-2 (FGF2) is a protein ligand, which exerts essential roles in development, angiogenesis, and tumor progression via activation of the downstream signaling cascades. Accumulating evidence has demonstrated that FGF2 is involved in the progression of ovarian cancer, providing a novel potential target for ovarian cancer therapy. In this study, we showed that FGF2 is significantly increased in ovarian tumors, and is negatively associated with the overall survival of ovarian cancer by database analysis. A short peptide obtained from a heptapeptide phage display library suppressed FGF2-induced proliferation, migration, and invasion of the p53-null epithelial ovarian cancer (EOC) cells. Further investigations revealed that the short peptide antagonized the effects of FGF2 on G0/G1 to S cell phase promotion, cyclin D1 expression, and MAPK and Akt signaling activation, which might contribute to the mechanism underlying the inhibitory effects of the short peptide on the aggressive phenotype of the ovarian cancer cells triggered by FGF2. Moreover, the short peptide might have the potentials of reversing FGF2-induced resistance to the doxorubicin via downregulation of the antiapoptotic proteins and counteracting of the antiapoptotic effects of FGF2 on p53-null EOC cells. Taken together, the short peptide targeting FGF2 may provide a novel strategy for improving the therapeutic efficiency in a subset of EOC.

Prostate cancer (PCa) is the most common malignancy among men. Tumor metastasis and chemoresistance contribute to the major cause of the mortality. In this study, we compared the protein profiles of two prostate cancer cell lines with different metastatic potentials, and identified cofilin-1 (CFL1) was one of the most differentially expressed proteins between two cell lines. Further results suggested that cofilin-1 promoted the remodeling of F-actin cytoskeleton, and enhanced the proliferation, migration and invasion of the prostate cancer cells via activation of P38 MAPK signaling pathway. In addition, cofilin-1 elevated the expression and drug efflux activity of multidrug resistance protein 1 (MDR1) by P38 MAPK signaling pathway, resulting in decrease of the adriamycin-induced apoptosis as well as the lytic cell death, and the subsequent resistance against adriamycin. Collectively, cofilin-1 might serve as a novel target candidate for both inhibiting the metastasis and reversing the chemoresistance of PCa.

Aberrant over-expressions of FGF9 in gastric cancer (GC) and its high-affinity receptor FGFR3c in bladder cancer (BC) provide possibilities for the treatment of GC and BC via targeting FGF9. In this study, we isolated a novel FGF9-binding peptide (P4) by screening a phage display random heptapeptide library. Sequence comparison showed that P4 shared high homology with the conserved motif in the immunoglobulin-like (Ig-like) domain II∼III (D2-D3) linker of the FGF9 high-affinity receptor (FGFR3c). The interaction between P4 and FGF9 was confirmed by the surface plasmon resonance (SPR) assay. Functional analysis indicated that P4 counteracted FGF9-induced aggressive phenotype, including cell proliferation, migration, and invasion in vitro, as well as suppressed tumor growth in vivovia down-regulation of the MAPKs and Akt cascades. More importantly, we found that FGF9 served as an underlying mechanism of the chemoresistance in GC and BC cells, and P4 could increase the sensitivity to the chemical agent via antagonizing the suppression effects of FGF9 on cell apoptosis. Taken together, our study identified a novel binding peptide for FGF9, which may serve as a potential therapeutic agent for malignant tumors featured by abnormally up-regulation of FGF9.