Abstract
A combination of molecular-targeted cancer imaging and therapy is an emerging strategy to improve cancer diagnosis and minimize the side effects of conventional treatments. Here, we generated a recombinant protein, EC1-GLuc-p53C, by fusing EC1 peptide, an artificial ligand of ErbB2, with Gaussia luciferase (GLuc) and a p53-activating peptide, p53C. EC1-GLuc-p53C was expressed and purified from E. coli BL21. In vitro experiments showed that EC1-GLuc-p53c was stable in luminescent activity and selectively targeted ErbB2-overexpressing BT474 cells for bioluminescence imaging. Moreover, the internalized EC1-GLuc-p53C in BT474 cells exerted its function to reactivate p53 and significantly inhibited cellular proliferation. In tumor-bearing mice, the ErbB2-targeted bioluminescence imaging and therapeutic effect of EC1-GLuc-p53C were also observed specifically in BT474 tumors but not in MCF7 tumors, which does not overexpress ErbB2. Thus, the present study demonstrates EC1-GLuc-p53C to be an effective theranostic reagent targeting ErbB2 for bioluminescence imaging and cancer therapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / isolation & purification
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Disease Models, Animal
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Female
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Gene Expression
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Heterografts
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Humans
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Ligands
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Luminescent Measurements*
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Mice
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Mice, Nude
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Molecular Imaging*
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Molecular Targeted Therapy
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Neoplasms / diagnosis
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Neoplasms / metabolism*
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Neoplasms / therapy
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Optical Imaging
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Protein Binding
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Protein Stability
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Receptor, ErbB-2 / antagonists & inhibitors
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Receptor, ErbB-2 / genetics
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Receptor, ErbB-2 / metabolism*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / isolation & purification
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Recombinant Fusion Proteins / metabolism*
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Recombinant Fusion Proteins / pharmacology
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Tumor Burden / drug effects
Substances
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Antineoplastic Agents
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Ligands
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Recombinant Fusion Proteins
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Receptor, ErbB-2
Grants and funding
This work was supported by grant-in-aid for Young Scientists (B) from the Ministry of Education, Science, Sports and Culture of Japan (No: 21790202,
http://www.waseda.jp/rps/en/manual/kakenhi_honbun.html) and by Grant-in-aid for Scientific Research from the Japan Society for the Promotion of Science (No: 22.00119,
http://www.jsps.go.jp/english/e-grants/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.