title: 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 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.
authors.affiliation: Department of Pain of Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Central Laboratory, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Xihan
authors.initials: X
authors.lastname: Li
authors.affiliation: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Huizi
authors.initials: H
authors.lastname: Sha
authors.affiliation: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Lianru
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Bian
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Jiangsu Diabetes Center, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, China. baoruiliu@nju.edu.cn.
authors.forename: Baorui
authors.initials: B
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000737:chemistry / Q000235:genetics; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C569656:N-end cysteine peptide tumor-homing peptide; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand