Open Access

P18 peptide, a functional fragment of pigment epithelial-derived factor, inhibits angiogenesis in hepatocellular carcinoma via modulating VEGF/VEGFR2 signalling pathway

  • Authors:
    • Xin Wang
    • Peng Xiu
    • Fuhai Wang
    • Jingtao Zhong
    • Honglong Wei
    • Zongzhen Xu
    • Feng Liu
    • Jie Li
  • View Affiliations

  • Published online on: June 14, 2017     https://doi.org/10.3892/or.2017.5719
  • Pages: 755-766
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The P18 peptide is a functional fragment of pigment epithelial-derived factor (PEDF), which is an endogenic angiogenesis inhibitor. This study sought to determine the anti-angiogenic bioactivity of the P18 peptide in hepato­cellular carcinoma (HCC) and to elucidate the underlying mechanism. Xenograft tumour growth assays demonstrated the P18 peptide suppressed angiogenesis of HCC in vivo. Wound healing, Transwell and Matrigel-culture assays indicated that the P18 peptide inhibited the cell migration and tube formation of endothelial cells (ECs) in vitro. Cell viability and apoptosis assessed by Cell Counting Kit-8 (CCK-8) and flow cytometry assays suggested that the P18 peptide inhibited angiogenesis by inducing apoptosis of ECs. Angiogenesis- and signal transduction-associated molecules analysed by western blot demonstrated that the P18 peptide targets vascular endothelial cell growth factor receptor 2 (VEGFR2) on ECs. In conclusion, by inhibiting the phosphorylation of VEGFR2, the P18 peptide modulates signalling transduction between VEGF/VEGFR2 and suppresses activation of the PI3K/Akt cascades, leading to an increase in mitochondrial-mediated apoptosis and anti-angiogenic activity. This bioactivity of the P18 peptide may represent a novel therapeutic strategy for the treatment of HCC.
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August-2017
Volume 38 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Wang X, Xiu P, Wang F, Zhong J, Wei H, Xu Z, Liu F and Li J: P18 peptide, a functional fragment of pigment epithelial-derived factor, inhibits angiogenesis in hepatocellular carcinoma via modulating VEGF/VEGFR2 signalling pathway. Oncol Rep 38: 755-766, 2017.
APA
Wang, X., Xiu, P., Wang, F., Zhong, J., Wei, H., Xu, Z. ... Li, J. (2017). P18 peptide, a functional fragment of pigment epithelial-derived factor, inhibits angiogenesis in hepatocellular carcinoma via modulating VEGF/VEGFR2 signalling pathway. Oncology Reports, 38, 755-766. https://doi.org/10.3892/or.2017.5719
MLA
Wang, X., Xiu, P., Wang, F., Zhong, J., Wei, H., Xu, Z., Liu, F., Li, J."P18 peptide, a functional fragment of pigment epithelial-derived factor, inhibits angiogenesis in hepatocellular carcinoma via modulating VEGF/VEGFR2 signalling pathway". Oncology Reports 38.2 (2017): 755-766.
Chicago
Wang, X., Xiu, P., Wang, F., Zhong, J., Wei, H., Xu, Z., Liu, F., Li, J."P18 peptide, a functional fragment of pigment epithelial-derived factor, inhibits angiogenesis in hepatocellular carcinoma via modulating VEGF/VEGFR2 signalling pathway". Oncology Reports 38, no. 2 (2017): 755-766. https://doi.org/10.3892/or.2017.5719