A novel peptide specifically binding to interleukin-6 receptor (gp80) inhibits angiogenesis and tumor growth

Jen Liang Su, Kuo Pao Lai, Chi An Chen, Ching Yao Yang, Pei Sheng Chen, Chiao Chia Chang, Chia Hung Chou, Chi Lun Hu, Min Liang Kuo, Chang Yao Hsieh, Lin Hung Wei

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)

Abstract

Experimental and clinical findings support the essential role of interleukin (IL)-6 in the pathogenesis of various human cancers and provide a rationale for targeted therapeutic investigations. A novel peptide, S7, which selectively binds to IL-6 receptor (IL-6R) α chain (gp80) and broadly inhibits IL-6-mediated events, was identified using phage display library screening. The synthetic S7 peptide specifically bound to soluble IL-6R as well as cognate human IL-6Rα, resulting in a dose-dependent blockade of the interaction between IL-6 and IL-6Rα. S7 peptide prevents IL-6-mediated survival signaling and sensitizes cervical cancer cells to chemotherapeutic compounds in vitro. The in vitro analysis of antiangiogenic activity showed that S7 peptide substantially inhibits IL-6-induced vascular endothelial growth factor-A expression and angiogenesis in different cancer cell lines. Furthermore, S7 peptide was bioavailable in vivo, leading to a significant suppression of IL-6-induced vascular endothelial growth factor-mediated cervical tumor growth in severe combined immunodeficient mice. These observations show the feasibility of targeting IL-6/IL-6R interaction using the small peptide and highlight its potential in the clinical applications.

Original languageEnglish
Pages (from-to)4827-4835
Number of pages9
JournalCancer Research
Volume65
Issue number11
DOIs
Publication statusPublished - 2005 Jun 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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