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Article

A ligand-based and enediyne-energized bispecific fusion protein targeting epidermal growth factor receptor and insulin-like growth factor-1 receptor shows potent antitumor efficacy against esophageal cancer

  • Authors:
    • Hai-Ying Cao
    • Xiao-Fang Guo
    • Xiao-Fei Zhu
    • Sai-Sai Li
    • Yong-Su Zhen
  • View Affiliations / Copyright

    Affiliations: School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Perking Union Medical College, Beijing 100050, P.R. China
  • Pages: 3329-3340
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    Published online on: April 27, 2017
       https://doi.org/10.3892/or.2017.5606
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Abstract

Recent studies have revealed that the epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) are overexpressed in various types of human tumors and are attractive targets for anticancer drugs. In the present study, the expression of EGFR and IGF-1R in esophageal squamous cell carcinoma (ESCC) and adjacent normal tissues in a tissue microarray was firstly detected by immunohistochemical staining. In addition, their co-overexpression was observed in 48 out of 75 (64%) patients. Based on the findings, the antitumor activity of an EGFR/IGF-1R bispecific and enediyne-energized fusion protein EGF-LDP-IGF-AE, which we constructed recently by fusing two ligands (EGF and IGF-1) with an enediyne antibiotic lidamycin (LDM), on ESCC were evaluated. Binding assay indicated that the EGF-LDP-IGF protein bound to esophageal cancer cells, and then internalized into the cytoplasm. In vitro, the enediyne‑energized fusion protein EGF-LDP-IGF-AE exhibited extremely potent cytotoxicity to ESCC cells with IC50 values between 10-10 and 10-15 mol/l. In vivo, EGF-LDP‑IGF-AE also markedly suppressed the growth of human KYSE450 xenografts by 75.1% when administered at 0.3 mg/kg in a nude mouse model, and its efficacy was significantly higher than that of LDM (at maximum tolerated dosage) and mono-specific counterparts. In addition, EGF-LDP-IGF-AE arrested cell cycle progression and it concentration-dependently induced cell apoptosis as well as inhibited the activation of EGFR/IGF-1R and two major downstream signaling pathways (PI3K/AKT and RAS/MAPK). These data imply the potential clinical application of EGF-LDP-IGF-AE for ESCC patients with EGFR and/or IGF-1R overexpression.
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Copy and paste a formatted citation
Spandidos Publications style
Cao H, Guo X, Zhu X, Li S and Zhen Y: A ligand-based and enediyne-energized bispecific fusion protein targeting epidermal growth factor receptor and insulin-like growth factor-1 receptor shows potent antitumor efficacy against esophageal cancer. Oncol Rep 37: 3329-3340, 2017.
APA
Cao, H., Guo, X., Zhu, X., Li, S., & Zhen, Y. (2017). A ligand-based and enediyne-energized bispecific fusion protein targeting epidermal growth factor receptor and insulin-like growth factor-1 receptor shows potent antitumor efficacy against esophageal cancer. Oncology Reports, 37, 3329-3340. https://doi.org/10.3892/or.2017.5606
MLA
Cao, H., Guo, X., Zhu, X., Li, S., Zhen, Y."A ligand-based and enediyne-energized bispecific fusion protein targeting epidermal growth factor receptor and insulin-like growth factor-1 receptor shows potent antitumor efficacy against esophageal cancer". Oncology Reports 37.6 (2017): 3329-3340.
Chicago
Cao, H., Guo, X., Zhu, X., Li, S., Zhen, Y."A ligand-based and enediyne-energized bispecific fusion protein targeting epidermal growth factor receptor and insulin-like growth factor-1 receptor shows potent antitumor efficacy against esophageal cancer". Oncology Reports 37, no. 6 (2017): 3329-3340. https://doi.org/10.3892/or.2017.5606
Copy and paste a formatted citation
x
Spandidos Publications style
Cao H, Guo X, Zhu X, Li S and Zhen Y: A ligand-based and enediyne-energized bispecific fusion protein targeting epidermal growth factor receptor and insulin-like growth factor-1 receptor shows potent antitumor efficacy against esophageal cancer. Oncol Rep 37: 3329-3340, 2017.
APA
Cao, H., Guo, X., Zhu, X., Li, S., & Zhen, Y. (2017). A ligand-based and enediyne-energized bispecific fusion protein targeting epidermal growth factor receptor and insulin-like growth factor-1 receptor shows potent antitumor efficacy against esophageal cancer. Oncology Reports, 37, 3329-3340. https://doi.org/10.3892/or.2017.5606
MLA
Cao, H., Guo, X., Zhu, X., Li, S., Zhen, Y."A ligand-based and enediyne-energized bispecific fusion protein targeting epidermal growth factor receptor and insulin-like growth factor-1 receptor shows potent antitumor efficacy against esophageal cancer". Oncology Reports 37.6 (2017): 3329-3340.
Chicago
Cao, H., Guo, X., Zhu, X., Li, S., Zhen, Y."A ligand-based and enediyne-energized bispecific fusion protein targeting epidermal growth factor receptor and insulin-like growth factor-1 receptor shows potent antitumor efficacy against esophageal cancer". Oncology Reports 37, no. 6 (2017): 3329-3340. https://doi.org/10.3892/or.2017.5606
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