sTRAIL-iRGD is a promising therapeutic agent for gastric cancer treatment

Abstract Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells and augments chemotherapeutics in vivo. Here, we developed sTRAIL-iRGD, a recombinant protein consisting of sTRAIL fused to CRGDKGPDC, a C-terminal end binding peptide with an integrin-binding argi...

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Autores principales:	Ying Huang, Xihan Li, Huizi Sha, Lianru Zhang, Xinyu Bian, Xiao Han, Baorui Liu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ab725ef9bbca40aba2422b2ad0085119
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spelling	oai:doaj.org-article:ab725ef9bbca40aba2422b2ad00851192021-12-02T12:32:34ZsTRAIL-iRGD is a promising therapeutic agent for gastric cancer treatment10.1038/s41598-017-00688-62045-2322https://doaj.org/article/ab725ef9bbca40aba2422b2ad00851192017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00688-6https://doaj.org/toc/2045-2322Abstract Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells and augments chemotherapeutics in vivo. Here, we developed sTRAIL-iRGD, a recombinant protein consisting of sTRAIL fused to CRGDKGPDC, a C-terminal end binding peptide with an integrin-binding arginine-glycine-aspartic acid (iRGD) motif. CRGDKGPDC is a tumor-homing peptide with high penetration into tumor tissue and cells. We found that sTRAIL-iRGD internalized into cultured gastric cancer tumor cells and localized to both the tumor mass in vivo and three-dimensional multicellular spheroids in vitro. sTRAIL-iRGD had an antitumor effect in tumor cell lines, multicellular spheroids and nude mice with tumors. Repeated treatment with sTRAIL-iRGD reduced tumor growth and volume in vivo. Mice treated with sTRAIL-iRGD and paclitaxel (PTX) in combination showed no sign of sTRAIL-iRGD-related liver toxicity. Our data suggest that sTRAIL-iRGD is a promising anti-gastric cancer agent with high selectivity and limited systemic toxicity.Ying HuangXihan LiHuizi ShaLianru ZhangXinyu BianXiao HanBaorui LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ying Huang Xihan Li Huizi Sha Lianru Zhang Xinyu Bian Xiao Han Baorui Liu sTRAIL-iRGD is a promising therapeutic agent for gastric cancer treatment
description	Abstract Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells and augments chemotherapeutics in vivo. Here, we developed sTRAIL-iRGD, a recombinant protein consisting of sTRAIL fused to CRGDKGPDC, a C-terminal end binding peptide with an integrin-binding arginine-glycine-aspartic acid (iRGD) motif. CRGDKGPDC is a tumor-homing peptide with high penetration into tumor tissue and cells. We found that sTRAIL-iRGD internalized into cultured gastric cancer tumor cells and localized to both the tumor mass in vivo and three-dimensional multicellular spheroids in vitro. sTRAIL-iRGD had an antitumor effect in tumor cell lines, multicellular spheroids and nude mice with tumors. Repeated treatment with sTRAIL-iRGD reduced tumor growth and volume in vivo. Mice treated with sTRAIL-iRGD and paclitaxel (PTX) in combination showed no sign of sTRAIL-iRGD-related liver toxicity. Our data suggest that sTRAIL-iRGD is a promising anti-gastric cancer agent with high selectivity and limited systemic toxicity.
format	article
author	Ying Huang Xihan Li Huizi Sha Lianru Zhang Xinyu Bian Xiao Han Baorui Liu
author_facet	Ying Huang Xihan Li Huizi Sha Lianru Zhang Xinyu Bian Xiao Han Baorui Liu
author_sort	Ying Huang
title	sTRAIL-iRGD is a promising therapeutic agent for gastric cancer treatment
title_short	sTRAIL-iRGD is a promising therapeutic agent for gastric cancer treatment
title_full	sTRAIL-iRGD is a promising therapeutic agent for gastric cancer treatment
title_fullStr	sTRAIL-iRGD is a promising therapeutic agent for gastric cancer treatment
title_full_unstemmed	sTRAIL-iRGD is a promising therapeutic agent for gastric cancer treatment
title_sort	strail-irgd is a promising therapeutic agent for gastric cancer treatment
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ab725ef9bbca40aba2422b2ad0085119
work_keys_str_mv	AT yinghuang strailirgdisapromisingtherapeuticagentforgastriccancertreatment AT xihanli strailirgdisapromisingtherapeuticagentforgastriccancertreatment AT huizisha strailirgdisapromisingtherapeuticagentforgastriccancertreatment AT lianruzhang strailirgdisapromisingtherapeuticagentforgastriccancertreatment AT xinyubian strailirgdisapromisingtherapeuticagentforgastriccancertreatment AT xiaohan strailirgdisapromisingtherapeuticagentforgastriccancertreatment AT baoruiliu strailirgdisapromisingtherapeuticagentforgastriccancertreatment
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sTRAIL-iRGD is a promising therapeutic agent for gastric cancer treatment

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