Sendai virus-mediated gene transfer of the c-myc suppressor far-upstream element-binding protein-interacting repressor suppresses head and neck cancer

• Published in: Gene therapy Vol. 22; no. 4; pp. 297 - 304
• Main Authors: Tanaka, N, Araki, K, Mizokami, D, Miyagawa, Y, Yamashita, T, Tomifuji, M, Ueda, Y, Inoue, M, Matsushita, K, Nomura, F, Shimada, H, Shiotani, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2015; Nature Publishing Group
• Subjects: 13/2; 13/51; 14/35; 38/44; 631/1647/1511; 631/61/2300/1514; 631/67/1536; 64/60; 692/699/67/1536; 82/80; 96/1; Analysis; Animal models; Animals; Antitumor activity; Apoptosis; Binding sites; Biomedical and Life Sciences; Biomedicine; c-Myc protein; Cancer; Carcinoma; Cell Biology; Cell Line; Cytotoxicity; Development and progression; Female; Fluorescence; Fusion protein; Gene Expression; Gene Therapy; Gene Transfer Techniques; Genes; Genetic aspects; Genetic research; Genetic Therapy; Genetic transformation; Genetic Vectors; Green fluorescent protein; Guanine Nucleotide Exchange Factors - metabolism; Head & neck cancer; Head and neck cancer; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - therapy; Health aspects; Heterografts; Human Genetics; Humans; Medical schools; Mice; Multiplicity of infection; Myc protein; Nanotechnology; Neoplasm Transplantation; Novels; Oncology, Experimental; original-article; Protein binding; Proteins; Proto-Oncogene Proteins c-myc - metabolism; Scientific equipment industry; Sendai virus; Sendai virus - metabolism; Squamous cell carcinoma; Transcription factors; Tumor suppression; Tumors; Xenografts; United States; Japan
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/gt.2014.123

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.