The recombinant EGFR/CD13 bi-targeted fusion protein induces apoptosis and blocks tube formation

Sheng,Weijin; Gong,Jianhua; Jiang,Min; Zhen,Yongsu

doi:10.3892/or.2017.6053

The recombinant EGFR/CD13 bi-targeted fusion protein induces apoptosis and blocks tube formation

Authors:
- Weijin Sheng
- Jianhua Gong
- Min Jiang
- Yongsu Zhen
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Affiliations: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China
Published online on: October 23, 2017 https://doi.org/10.3892/or.2017.6053
Pages: 3507-3514

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Abstract

Previously it was shown that the recombinant EGFR/CD13 bi-targeted fusion protein ER(Fv)‑LDP-NGR which consists of an anti‑EGFR scFv antibody fragment, a tri‑cyclic NGR peptide, and a lidamycin-derived apoprotein, inhibited the proliferation of cancer cells and markedly suppressed tumor growth of breast carcinoma MCF-7 xenografts in athymic mice. This study investigated the mechanism of action of the fusion protein. Human breast cancer MCF-7 cells, lung adenocarcinoma A549 cells, and microvascular endothelial HMEC‑1 cells were used for a series of assays and determinations. ER(Fv)‑LDP-NGR downregulated the transcription and expression of the target proteins EGFR and CD13, and interfered with the intracellular EGFR signaling pathway, cell cycle signaling pathway and apoptotic pathway. It induced apoptosis, inhibited proliferation, caused cell cycle G2/M phase arrest, and suppressed cell migration. Accompanied by weakening the capability to degrade extracellular matrix, ER(Fv)‑LDP-NGR depressed the invasion capacity of cancer cells. In addition, ER(Fv)‑LDP-NGR prevented microvascular endothelial cells from tube formation, which is closely related to angiogenesis. In conclusion, the EGFR/CD13 bi-targeted fusion protein ER(Fv)‑LDP-NGR displays multi-functional characteristics, acting on both cancer cells and endothelial cells. It might be an effective agent for targeted cancer therapy.

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