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Journal of Cancer Research and Clinical Oncology

, Volume 138, Issue 8, pp 1321–1328 | Cite as

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

  • Yonglin Yu
  • Susu Gao
  • Quchou Li
  • Cong Wang
  • Xinqiang Lai
  • Xilei Chen
  • Ruixue Wang
  • Jingfang Di
  • Tao Li
  • Wenhui Wang
  • Xiaoping Wu
Original Paper

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.

Keywords

FGF2-binding peptide Proliferation Angiogenesis Melanoma 

Notes

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (30973671, 81071800), the Natural Science Foundation of Zhejiang Province of China (Y2090292), the Natural Science Foundation of Guangdong Province of China (9151064001000031), the Science and Technology Planning Project of Wenzhou (Y20090244), the Fundamental Research Funds for the Central Universities (X. P. Wu), Guangdong Provincial “Thousand-Hundred-Ten Talent Project” (X. P. Wu), and Guangdong Provincial Key Discipline in Biochemistry and Molecular biology.

Conflict of interest

All authors declare that there are no potential conflicts of interest.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Yonglin Yu
    • 1
  • Susu Gao
    • 1
  • Quchou Li
    • 1
  • Cong Wang
    • 2
  • Xinqiang Lai
    • 1
  • Xilei Chen
    • 1
  • Ruixue Wang
    • 1
  • Jingfang Di
    • 1
  • Tao Li
    • 1
  • Wenhui Wang
    • 1
  • Xiaoping Wu
    • 1
    • 2
  1. 1.Institute of Tissue Transplantation and ImmunologyJinan UniversityGuangzhouChina
  2. 2.School of Pharmaceutical ScienceWenzhou Medical CollegeWenzhouChina

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