title: The FGF2-binding peptide P7 inhibits melanoma growth in vitro and in vivo.
abstract: OBJECTIVE
  Melanoma is a malignant tumor and causes majority of deaths related to skin cancer. Fibroblast growth factor 2 (FGF2) greatly contributes to melanoma growth and progress. In this paper, we attempt to evaluate the therapeutic potential of FGF2-binding peptide (named P7) using as a potent FGF2 antagonist via exploration of its antitumor effect on melanoma in vitro and in vivo.
  
  
  METHODS
  Cell viability was measured by WST-1. Cell cycle progression was determined by propidium iodide staining and flow cytometry. Western blotting was carried out to detect the activation of Erk1/2, P38, Akt, and MEK, and the expression of apoptosis-associated proteins. The influence of P7 on FGF2 internalization was assessed by separation of nuclear and cytoplasmic protein fractions followed by Western blotting. Female C57BL/6 mice bearing xenograft melanoma were established and used to evaluate the antitumor effect of P7 in vivo.
  
  
  RESULTS
  In this study, we first proved that P7 peptides significantly inhibited proliferation of FGF2-induced melanoma cell line B16-F10. Further investigations revealed that the mechanisms of P7 peptides inhibiting cell proliferation of melanoma cells stimulated with FGF2 in vitro involved cell cycle arrest at the G0/G1 phase, blockade of the activation of Erk1/2, P38, and Akt cascades, and inhibition of FGF2 internalization. Finally, treatment of P7 peptides in a murine melanoma model resulted in significant inhibition of tumor growth and angiogenesis in vivo, which was associated with blockade of mitogen-activated protein kinase signal activation, and suppression of the expressions of anti-apoptotic Bcl-2 protein and angiogenic factor in the melanoma tumors.
  
  
  CONCLUSIONS
  The FGF2-binding peptide with potent antiproliferation and anti-angiogenic activity may have therapeutic potential in melanoma.
authors.affiliation: Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632, China.
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Yu
authors.forename: Susu
authors.initials: S
authors.lastname: Gao
authors.forename: Quchou
authors.initials: Q
authors.lastname: Li
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.forename: Xinqiang
authors.initials: X
authors.lastname: Lai
authors.forename: Xilei
authors.initials: X
authors.lastname: Chen
authors.forename: Ruixue
authors.initials: R
authors.lastname: Wang
authors.forename: Jingfang
authors.initials: J
authors.lastname: Di
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Wenhui
authors.initials: W
authors.lastname: Wang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D005434:Flow Cytometry; D016193:G1 Phase / Q000235:genetics; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D009842:Oligopeptides; D016222:Fibroblast Growth Factor 2; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases