Oncotarget

Research Papers:

HER2-siRNA delivered by EGFR-specific single chain antibody inhibits NSCLC cell proliferation and tumor growth

Yuan Lu, Yuan Wang, Mi Zhang, Li Liu, Fakai Li, Jian Zhang, Mingxiang Ye, Hu Zhao, Jing Zhao, Bo Yan, Angang Yang, Rui Zhang _, Xia Li and Xinling Ren

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Oncotarget. 2016; 7:23594-23607. https://doi.org/10.18632/oncotarget.8053

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Abstract

Yuan Lu1,*, Yuan Wang1,*, Mi Zhang3,*, Li Liu1,2, Fakai Li1, Jian Zhang1, Mingxiang Ye1, Hu Zhao4, Jing Zhao5, Bo Yan5, Angang Yang6, Rui Zhang5, Xia Li5, Xinling Ren1

1Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, China

2Department of Geriatrics, Xianyang Central Hospital, Xianyang, China

3Department of Respiratory Medicine, PLA General Hospital, Beijing, China

4Organ Transplant Institute, Fuzhou General Hospital (DongFang Hospital), Xiamen University, Fuzhou, China

5State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi’an, China

6State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi’an, China

*These authors have contributed equally to this work

Correspondence to:

Rui Zhang, email: ruizhang@fmmu.edu.cn

Xia Li, email: lixia@fmmu.edu.cn

Xinling Ren, email: majrenxl@fmmu.edu.cn

Keywords: non-small cell lung cancer, EGFR, HER2, single-chain viable-fragment antibody, small interfering RNA

Received: September 30, 2015     Accepted: February 29, 2016     Published: March 14, 2016

ABSTRACT

Overexpression of human epidermal growth factor receptor type2 (HER2) is closely associated with aggressive progression and poor prognosis in non-small cell lung cancer (NSCLC). Here, we generated an EGFR-scFv-arginine nonamer peptide fusion protein (scFv-9R) as a cargo to deliver HER2 specific siRNA into HER2-positive NSCLC cells both in vitro and in vivo. HER2-siRNAs delivered by scFv-9R effeciently silenced HER2 expression in EGFR-positive NSCLC cells, and consequently resulted in G1 arrest and cell growth inhibition. Importantly, intravenous injection of scFv-9R/HER2-siRNA complex markedly suppressed growth of EGFR-positive NSCLC xenograft in nude mice, resulting from downregulated HER2 expression, reduced cell proliferation and enhanced cell apoptosis. Collectively, our study provides a novel therapeutic strategy for the treatment of EGFR-positive, HER2-overexpressed NSCLC.


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