title: HER2-siRNA delivered by EGFR-specific single chain antibody inhibits NSCLC cell proliferation and tumor growth.
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.
authors.affiliation: Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, PLA General Hospital, Beijing, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.|Department of Geriatrics, Xianyang Central Hospital, Xianyang, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Fakai
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Mingxiang
authors.initials: M
authors.lastname: Ye
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital (DongFang Hospital), Xiamen University, Fuzhou, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, China.
authors.forename: Angang
authors.initials: A
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Xinling
authors.initials: X
authors.lastname: Ren
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000517:prevention & control / Q000556:secondary; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000517:prevention & control / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000517:prevention & control / Q000556:secondary; D002453:Cell Cycle; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D057127:Single-Chain Antibodies / Q000494:pharmacology*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D057127:Single-Chain Antibodies; C512478:EGFR protein, human; C508053:ERBB2 protein, human
keywords: EGFR; HER2; non-small cell lung cancer; single-chain viable-fragment antibody; small interfering RNA