Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 77, Issue -, Pages 60-72Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejps.2015.05.020
Keywords
Recombinant protein; iRGD; Anti-EGFR single-domain antibody; Multicellular spheroids; Gastric cancer; Paclitaxel
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Funding
- National Key Specialty of Clinical Oncology [120131544]
- Key Medical Oncology Subject of Jiangsu Province [XK201103]
- National Natural Science Foundation of China [81472216, 81302053]
- Nanjing Medical Science and Technique Development Foundation
- Nanjing Medical Science and Technique Development Foundation (Outstanding Youth Foundation) [JQX12003]
- Scientific Research Foundation of Graduate School of Nanjing University [2013CL15]
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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. (C) 2015 Elsevier B.V. All rights reserved.
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