HER2-siRNA delivered by EGFR-specific single chain antibody inhibits NSCLC cell proliferation and tumor growth
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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
Rui Zhang, email: email@example.com
Xia Li, email: firstname.lastname@example.org
Xinling Ren, email: email@example.com
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
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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