title: A tumor-penetrating recombinant protein anti-EGFR-iRGD enhance efficacy of paclitaxel in 3D multicellular spheroids and gastric cancer in vivo.
abstract: It has been a major challenge for drug penetration in solid tumor tissues because of the complicated tumor microenvironment. We have previously constructed a protein of bispecific targets and high permeability named anti-EGFR-iRGD and investigated its inhibiting cell proliferation of gastric cancer. Paclitaxel (PTX) is widely used for treating various kinds of cancer. In this paper, we investigated the effects of anti-EGFR-iRGD in combination with chemotherapeutic drugs including PTX in epidermal growth factor receptor highly expressing gastric cancer. We demonstrated the therapeutic efficacy of PTX combined with anti-EGFR-iRGD on monolayer cells (2D), multicellular spheroids (3D) and tumor-bearing mice for the first time and investigated the mechanism of this synergy effect. Our results provide impetus for further studies to use anti-EGFR-iRGD with standard cytotoxic treatment regimens for enhancing therapy of gastric cancer patients.
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China.
authors.forename: Huizi
authors.initials: H
authors.lastname: Sha
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China.
authors.forename: Rutian
authors.initials: R
authors.lastname: Li
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Bian
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: MOE Key Laboratory of High Performance Polymer Materials and Technology, Jiangsu Key Laboratory for Nanotechnology and Department of Polymer Science & Engineering, College of Chemistry & Chemical Engineering, Nanjing University, Nanjing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Radiology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xin
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Kong
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Qian
authors.affiliation: MOE Key Laboratory of High Performance Polymer Materials and Technology, Jiangsu Key Laboratory for Nanotechnology and Department of Polymer Science & Engineering, College of Chemistry & Chemical Engineering, Nanjing University, Nanjing, China.
authors.forename: Xiqun
authors.initials: X
authors.lastname: Jiang
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China. Electronic address: hwj19987@sina.com.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Hu
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China. Electronic address: baoruiliu@nju.edu.cn.
authors.forename: Baorui
authors.initials: B
authors.lastname: Liu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D066246:ErbB Receptors / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D041681:NIH 3T3 Cells; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D017239:Paclitaxel / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; C047981:arginyl-glycyl-aspartic acid; D066246:ErbB Receptors; D017239:Paclitaxel
keywords: 5-Fluorouracil (PubChem CID: 3385); Anti-EGFR single-domain antibody; Fluorescein isothiocyanate (PubChem CID: 18730); Gastric cancer; Irinotecan (PubChem CID: 60838); Multicellular spheroids; Paclitaxel; Paclitaxel (PubChem CID: 36314); Recombinant protein; iRGD