title: The HGF inhibitory peptide HGP-1 displays promising in vitro and in vivo efficacy for targeted cancer therapy.
abstract: 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.
authors.affiliation: Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.|Suzhou Institute of Nano-Tech and Nano-Bionics, CAS, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.|Suzhou Institute of Nano-Tech and Nano-Bionics, CAS, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Li
authors.affiliation: Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D019151:Peptide Library; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation; D011485:Protein Binding; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C000609487:HGF inhibitory peptide HGP-1, human; C066855:HGF protein, human; D019151:Peptide Library; D010455:Peptides; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: HGF targeting peptide; HGF/MET signaling pathway; cancer targeted therapy