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

// Yuan Lu 1, * , Yuan Wang 1, * , Mi Zhang 3, * , Li Liu 1, 2 , Fakai Li 1 , Jian Zhang 1 , Mingxiang Ye 1 , Hu Zhao 4 , Jing Zhao 5 , Bo Yan 5 , Angang Yang 6 , Rui Zhang 5 , Xia Li 5 , Xinling Ren 1 1 Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, China 2 Department of Geriatrics, Xianyang Central Hospital, Xianyang, China 3 Department of Respiratory Medicine, PLA General Hospital, Beijing, China 4 Organ Transplant Institute, Fuzhou General Hospital (DongFang Hospital), Xiamen University, Fuzhou, China 5 State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi’an, China 6 State 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.