title: Sendai virus-mediated gene transfer of the c-myc suppressor far-upstream element-binding protein-interacting repressor suppresses head and neck cancer.
abstract: Far-upstream element-binding protein-interacting repressor (FIR) is a transcription factor that inhibits c-Myc expression and has been shown to have antitumor effects in some malignancies. Here, we evaluated the antitumor effects of FIR using fusion gene-deleted Sendai virus (SeV/ΔF) as a nontransmissible vector against head and neck squamous cell carcinoma (HNSCC). Using in vitro and in vivo xenograft mouse models, we observed efficient expression of green fluorescent protein (GFP) following transduction with the SeV/ΔF vector encoding GFP (GFP-SeV/ΔF) into HNSCC cells. In vitro and in vivo studies revealed that administration of the FIR-encoded SeV/ΔF (FIR-SeV/ΔF) vector exerted significant antitumor effects, suppressed c-Myc expression and induced apoptosis in HNSCC. Additionally, the antitumor effects of FIR or the expression of GFP following administration of the FIR- or GFP-SeV/ΔF vector, respectively, were dependent on the multiplicity of infection or titer. Furthermore, the SeV/ΔF vector itself had no cytotoxic effects. Therefore, the SeV/ΔF vector may be safe and useful for the treatment of HNSCC, allowing for high-titer SeV/ΔF vector administration for anticancer gene therapy. In addition, SeV/ΔF vector-mediated FIR gene therapy demonstrated effective tumor suppression in HNSCC, suggesting that this therapy may have the potential for clinical use as a novel strategy for HNSCC treatment.
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, National Defense Medical College, Saitama, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, National Defense Medical College, Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Araki
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, National Defense Medical College, Saitama, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Mizokami
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, National Defense Medical College, Saitama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Miyagawa
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, National Defense Medical College, Saitama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, National Defense Medical College, Saitama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tomifuji
authors.affiliation: Department of Gene Medicine, DNAVEC Corporation, Ibaraki, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Department of Gene Medicine, DNAVEC Corporation, Ibaraki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Department of Molecular Diagnosis and Division of Clinical Genetics and Proteomics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsushita
authors.affiliation: Department of Molecular Diagnosis and Division of Clinical Genetics and Proteomics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Nomura
authors.affiliation: Department of Surgery, Toho University School of Medicine, Tokyo, Japan.
authors.forename: H
authors.identifier: 0000000219908217
authors.initials: H
authors.lastname: Shimada
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, National Defense Medical College, Saitama, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Shiotani
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D064593:Heterografts; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D029082:Sendai virus / Q000378:metabolism*
chemical_list: C577426:FARP2 protein, human; D020662:Guanine Nucleotide Exchange Factors; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc