Novel EGFR-targeted strategy with hybrid peptide against oesophageal squamous cell carcinoma

Epidermal growth factor receptor (EGFR) is a key molecule in the pathophysiology of oesophageal squamous cell carcinoma (OSCC). However, EGFR-targeted agents such as anti-EGFR antibody or tyrosine kinase inhibitors for OSCC have not demonstrated any clinical benefits. Recently, a novel chemotherapeu...

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Main Authors:	Kikuchi, Osamu, Ohashi, Shinya, Horibe, Tomohisa, Kohno, Masayuki, Nakai, Yukie, Miyamoto, Shin’ichi, Chiba, Tsutomu, Muto, Manabu, Kawakami, Koji
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4796678/

id	pubmed-4796678
recordtype	oai_dc
spelling	pubmed-47966782016-03-18 Novel EGFR-targeted strategy with hybrid peptide against oesophageal squamous cell carcinoma Kikuchi, Osamu Ohashi, Shinya Horibe, Tomohisa Kohno, Masayuki Nakai, Yukie Miyamoto, Shin’ichi Chiba, Tsutomu Muto, Manabu Kawakami, Koji Article Epidermal growth factor receptor (EGFR) is a key molecule in the pathophysiology of oesophageal squamous cell carcinoma (OSCC). However, EGFR-targeted agents such as anti-EGFR antibody or tyrosine kinase inhibitors for OSCC have not demonstrated any clinical benefits. Recently, a novel chemotherapeutic agent, EGFR(2R)-lytic hybrid peptide, a composite of EGFR-binding peptide and lytic peptide fragments, has been shown to exhibit a potent anti-tumour effect against cancers that express high EGFR levels. In this study, we investigated the validity of employing EGFR(2R)-lytic hybrid peptide against OSCC cells both in vitro and in vivo. Additionally, the toxicity of this peptide was assessed in mice. We found high EGFR expression levels on the cell surface of OSCC cells, and the EGFR-binding peptide fragment showed high affinity for OSCC cells. A potent cytotoxic effect was induced within 30 minutes by the exposure of OSCC cells to EGFR(2R)-lytic hybrid peptide. Furthermore, EGFR(2R)-lytic hybrid peptide markedly suppressed the tumour growth of OSCC cells in a xenograft model. Moreover, it did not cause any identifiable adverse effects in mice. Taken together, EGFR(2R)-lytic hybrid peptide was shown to be a valid therapeutic agent against OSCC, providing a crucial rationale regarding novel EGFR-targeted therapies against OSCC. Nature Publishing Group 2016-03-09 /pmc/articles/PMC4796678/ /pubmed/26956916 http://dx.doi.org/10.1038/srep22452 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kikuchi, Osamu Ohashi, Shinya Horibe, Tomohisa Kohno, Masayuki Nakai, Yukie Miyamoto, Shin’ichi Chiba, Tsutomu Muto, Manabu Kawakami, Koji
spellingShingle	Kikuchi, Osamu Ohashi, Shinya Horibe, Tomohisa Kohno, Masayuki Nakai, Yukie Miyamoto, Shin’ichi Chiba, Tsutomu Muto, Manabu Kawakami, Koji Novel EGFR-targeted strategy with hybrid peptide against oesophageal squamous cell carcinoma
author_facet	Kikuchi, Osamu Ohashi, Shinya Horibe, Tomohisa Kohno, Masayuki Nakai, Yukie Miyamoto, Shin’ichi Chiba, Tsutomu Muto, Manabu Kawakami, Koji
author_sort	Kikuchi, Osamu
title	Novel EGFR-targeted strategy with hybrid peptide against oesophageal squamous cell carcinoma
title_short	Novel EGFR-targeted strategy with hybrid peptide against oesophageal squamous cell carcinoma
title_full	Novel EGFR-targeted strategy with hybrid peptide against oesophageal squamous cell carcinoma
title_fullStr	Novel EGFR-targeted strategy with hybrid peptide against oesophageal squamous cell carcinoma
title_full_unstemmed	Novel EGFR-targeted strategy with hybrid peptide against oesophageal squamous cell carcinoma
title_sort	novel egfr-targeted strategy with hybrid peptide against oesophageal squamous cell carcinoma
description	Epidermal growth factor receptor (EGFR) is a key molecule in the pathophysiology of oesophageal squamous cell carcinoma (OSCC). However, EGFR-targeted agents such as anti-EGFR antibody or tyrosine kinase inhibitors for OSCC have not demonstrated any clinical benefits. Recently, a novel chemotherapeutic agent, EGFR(2R)-lytic hybrid peptide, a composite of EGFR-binding peptide and lytic peptide fragments, has been shown to exhibit a potent anti-tumour effect against cancers that express high EGFR levels. In this study, we investigated the validity of employing EGFR(2R)-lytic hybrid peptide against OSCC cells both in vitro and in vivo. Additionally, the toxicity of this peptide was assessed in mice. We found high EGFR expression levels on the cell surface of OSCC cells, and the EGFR-binding peptide fragment showed high affinity for OSCC cells. A potent cytotoxic effect was induced within 30 minutes by the exposure of OSCC cells to EGFR(2R)-lytic hybrid peptide. Furthermore, EGFR(2R)-lytic hybrid peptide markedly suppressed the tumour growth of OSCC cells in a xenograft model. Moreover, it did not cause any identifiable adverse effects in mice. Taken together, EGFR(2R)-lytic hybrid peptide was shown to be a valid therapeutic agent against OSCC, providing a crucial rationale regarding novel EGFR-targeted therapies against OSCC.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4796678/
_version_	1613553559282909184

Novel EGFR-targeted strategy with hybrid peptide against oesophageal squamous cell carcinoma

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