The FGF2-binding peptide P7 inhibits melanoma growth in vitro and in vivo.

Abstract

PURPOSE:

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: Yonglin Yu, Susu Gao, Quchou Li, Cong Wang, Xinqiang Lai, Xilei Chen, Ruixue Wang, Jingfang Di, Tao Li, Wenhui Wang, Xiaoping Wu
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 138 Issue 8 Pg. 1321-8 (Aug 2012) ISSN: 1432-1335 [Electronic] Germany
• PMID: 22481251 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Oligopeptides
• Fibroblast Growth Factor 2
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinases

Topics

• Amino Acid Sequence
• Animals
• Blotting, Western
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Endocytosis (drug effects)
• Female
• Fibroblast Growth Factor 2 (antagonists & inhibitors, metabolism, pharmacology)
• Flow Cytometry
• G1 Phase (genetics)
• Melanoma, Experimental (metabolism, pathology, prevention & control)
• Mice
• Mice, Inbred C57BL
• Mitogen-Activated Protein Kinases (metabolism)
• Neovascularization, Pathologic (metabolism, pathology, prevention & control)
• Oligopeptides (metabolism, pharmacology)
• Phosphorylation (drug effects)
• Protein Binding
• Proto-Oncogene Proteins c-akt (metabolism)
• Resting Phase, Cell Cycle (drug effects)
• Tumor Burden (drug effects)