The HGF inhibitory peptide HGP-1 displays promising in vitro and in vivo efficacy for targeted cancer therapy
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Lisha Chen1,2, Chunlin Li1,2, Yimin Zhu1
1Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
2Suzhou Institute of Nano-Tech and Nano-Bionics, CAS, University of Chinese Academy of Sciences, Beijing 100049, China
Yimin Zhu, e-mail: [email protected]
Keywords: HGF targeting peptide, HGF/MET signaling pathway, cancer targeted therapy
Received: January 29, 2015 Accepted: April 28, 2015 Published: May 11, 2015
HGF/MET pathway mediates cancer initiation and development. Thus, inhibition on HGF-initiated MET signaling pathway would provide a new approach to cancer targeted therapeutics. In our study, we identified a targeting peptide candidate binding to HGF which was named HGF binding peptide-1 (HGP-1) via bacterial surface display methods coupled with fluorescence-activated cell sorting (FACS). HGP-1 showed the moderate affinity when determined with surface plasmon resonance (SPR) technique and high specificity in binding to HGF while assessed by fluorescence-based ELISA assay. The results from MTT and in vitro migration assay indicated that HGF-dependent cell proliferation and migration could be inhibited by HGP-1. In vivo administration of HGP-1 led to an effective inhibitory effect on tumor growth in A549 tumor xenograft models. Moreover, findings from Western Blots revealed that HGP-1 could down-regulated the phosphorylation levels of MET and ERK1/2 initiated by HGF, which suggested that HGP-1 could disrupt the activation of HGF/MET signaling to influence the cell activity. All the data highlighted the potential of HGP-1 to be a potent inhibitor for HGF/MET signaling.
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