Targeting Interleukin-4 Receptor Alpha by Hybrid Peptide for Novel Biliary Tract Cancer Therapy

It is known that the interleukin-4 receptor α (IL-4Rα) is highly expressed on the surface of various human solid tumors. We previously designed novel IL-4Rα-lytic hybrid peptide composed of binding peptide to IL-4Rα and cell-lytic peptide and reported that the designed IL-4Rα-lytic hybrid peptide ex...

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Main Authors: Kahori Seto, Junichi Shoda, Tomohisa Horibe, Eiji Warabi, Masayuki Kohno, Toru Yanagawa, Hiroki Bukawa, Yasuni Nakanuma, Koji Kawakami
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:International Journal of Hepatology
Online Access:http://dx.doi.org/10.1155/2014/584650
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author Kahori Seto
Junichi Shoda
Tomohisa Horibe
Eiji Warabi
Masayuki Kohno
Toru Yanagawa
Hiroki Bukawa
Yasuni Nakanuma
Koji Kawakami
author_facet Kahori Seto
Junichi Shoda
Tomohisa Horibe
Eiji Warabi
Masayuki Kohno
Toru Yanagawa
Hiroki Bukawa
Yasuni Nakanuma
Koji Kawakami
author_sort Kahori Seto
collection DOAJ
description It is known that the interleukin-4 receptor α (IL-4Rα) is highly expressed on the surface of various human solid tumors. We previously designed novel IL-4Rα-lytic hybrid peptide composed of binding peptide to IL-4Rα and cell-lytic peptide and reported that the designed IL-4Rα-lytic hybrid peptide exhibited cytotoxic and antitumor activity both in vitro and in vivo against the human pancreatic cancer cells expressing IL-4Rα. Here, we evaluated the antitumor activity of the IL-4Rα-lytic hybrid peptide as a novel molecular targeted therapy for human biliary tract cancer (BTC). The IL-4Rα-lytic hybrid peptide showed cytotoxic activity in six BTC cell lines with a concentration that killed 50% of all cells (IC50) as low as 5 μM. We also showed that IL-4Rα-lytic hybrid peptide in combination with gemcitabine exhibited synergistic cytotoxic activity in vitro. In addition, intravenous administration of IL-4Rα-lytic hybrid peptide significantly inhibited tumor growth in a xenograft model of human BTC in vivo. Taken together, these results indicated that the IL-4Rα-lytic hybrid peptide is a potent agent that might provide a novel therapy for patients with BTC.
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institution Kabale University
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publishDate 2014-01-01
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spelling doaj-art-19f26fedd35b4540bf33fbdb8f966b8d2025-02-03T00:59:49ZengWileyInternational Journal of Hepatology2090-34482090-34562014-01-01201410.1155/2014/584650584650Targeting Interleukin-4 Receptor Alpha by Hybrid Peptide for Novel Biliary Tract Cancer TherapyKahori Seto0Junichi Shoda1Tomohisa Horibe2Eiji Warabi3Masayuki Kohno4Toru Yanagawa5Hiroki Bukawa6Yasuni Nakanuma7Koji Kawakami8Department of Oral and Maxillofacial Surgery, Clinical Sciences, University of Tsukuba, Ibaraki 305-8575, JapanMedical Science, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, JapanDepartment of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, JapanDivision of Biomedical Science, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, JapanDepartment of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, JapanDepartment of Oral and Maxillofacial Surgery, Clinical Sciences, University of Tsukuba, Ibaraki 305-8575, JapanDepartment of Oral and Maxillofacial Surgery, Clinical Sciences, University of Tsukuba, Ibaraki 305-8575, JapanDepartment of Human Pathology, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-1192, JapanDepartment of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, JapanIt is known that the interleukin-4 receptor α (IL-4Rα) is highly expressed on the surface of various human solid tumors. We previously designed novel IL-4Rα-lytic hybrid peptide composed of binding peptide to IL-4Rα and cell-lytic peptide and reported that the designed IL-4Rα-lytic hybrid peptide exhibited cytotoxic and antitumor activity both in vitro and in vivo against the human pancreatic cancer cells expressing IL-4Rα. Here, we evaluated the antitumor activity of the IL-4Rα-lytic hybrid peptide as a novel molecular targeted therapy for human biliary tract cancer (BTC). The IL-4Rα-lytic hybrid peptide showed cytotoxic activity in six BTC cell lines with a concentration that killed 50% of all cells (IC50) as low as 5 μM. We also showed that IL-4Rα-lytic hybrid peptide in combination with gemcitabine exhibited synergistic cytotoxic activity in vitro. In addition, intravenous administration of IL-4Rα-lytic hybrid peptide significantly inhibited tumor growth in a xenograft model of human BTC in vivo. Taken together, these results indicated that the IL-4Rα-lytic hybrid peptide is a potent agent that might provide a novel therapy for patients with BTC.http://dx.doi.org/10.1155/2014/584650
spellingShingle Kahori Seto
Junichi Shoda
Tomohisa Horibe
Eiji Warabi
Masayuki Kohno
Toru Yanagawa
Hiroki Bukawa
Yasuni Nakanuma
Koji Kawakami
Targeting Interleukin-4 Receptor Alpha by Hybrid Peptide for Novel Biliary Tract Cancer Therapy
International Journal of Hepatology
title Targeting Interleukin-4 Receptor Alpha by Hybrid Peptide for Novel Biliary Tract Cancer Therapy
title_full Targeting Interleukin-4 Receptor Alpha by Hybrid Peptide for Novel Biliary Tract Cancer Therapy
title_fullStr Targeting Interleukin-4 Receptor Alpha by Hybrid Peptide for Novel Biliary Tract Cancer Therapy
title_full_unstemmed Targeting Interleukin-4 Receptor Alpha by Hybrid Peptide for Novel Biliary Tract Cancer Therapy
title_short Targeting Interleukin-4 Receptor Alpha by Hybrid Peptide for Novel Biliary Tract Cancer Therapy
title_sort targeting interleukin 4 receptor alpha by hybrid peptide for novel biliary tract cancer therapy
url http://dx.doi.org/10.1155/2014/584650
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