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Enhanced binding to and killing of hepatocellular carcinoma cells in vitro by melittin when linked with a novel targeting peptide screened from phage display

Authors


Correspondence to: Wenyu Han, College of Animal Science and Veterinary Medicine, Jilin University, Xi'an Road 5333#, Changchun 130062, China. E-mail: hanwy@jlu.edu.cn.

Abstract

A random phage 12-mer peptide library and a whole-cell subtractive biopanning protocol against HepG2 cells were used to select a novel peptide-specific binding to hepatocellular carcinoma cells. As a result, peptide SLSLITMLKISR (AM-2) was screened as a novel homing peptide to hepatocellular carcinoma cells, tested by immunofluorescence and immunochemistry assays. Subsequently, peptide AM-2 was linked to melittin by A(EAAAK)2A, and the antitumor effect of this ligation product was detected by MTT assay, fluorescence-activated cell sorting, and scanning electron microscopy methods. Results of cell growth inhibition tests confirmed that the affinity of melittin was increased after being incorporated into AM-2, and AM-2-melittin specifically targeted and killed HepG2 cells in vitro. Thus, AM-2 is a valuable ligand for tumor targeting, which leads to increased binding and killing effect of hepatocellular carcinoma cells in vitro when ligated to melittin, and AM-2-melittin has a clinical potential application as target agents for the treatment of human hepatocellular carcinoma. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.

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