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

Gene Therapy volume 22, pages 297–304 (2015)Cite this article

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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.

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Acknowledgements

We thank Dr T Ota for providing the HSC-3-M3 cell line. A part of this paper was presented in July 2012 at the 8th International Conference on Head and Neck Cancer in Toronto, Canada. This work was supported by a Special Research Grant on Defense Medicine from the Ministry of Defense of Japan, Grant-in-Aid for Scientific Research (C) (JSPS KAKENHI Nos. 23592544, 23592545, 25462699 and 26462627) and Grant-in-Aid for Challenging Exploratory Research (JSPS KAKENHI No. 25670723).

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Authors and Affiliations

  1. Department of Otorhinolaryngology – Head and Neck Surgery, National Defense Medical College, Saitama, Japan

    N Tanaka, K Araki, D Mizokami, Y Miyagawa, T Yamashita, M Tomifuji & A Shiotani

  2. Department of Gene Medicine, DNAVEC Corporation, Ibaraki, Japan

    Y Ueda & M Inoue

  3. Department of Molecular Diagnosis and Division of Clinical Genetics and Proteomics, Chiba University Graduate School of Medicine, Chiba, Japan

    K Matsushita & F Nomura

  4. Department of Surgery, Toho University School of Medicine, Tokyo, Japan

    H Shimada

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  1. N Tanaka
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  3. D Mizokami
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Correspondence to K Araki.

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Tanaka, N., Araki, K., Mizokami, D. et al. Sendai virus-mediated gene transfer of the c-myc suppressor far-upstream element-binding protein-interacting repressor suppresses head and neck cancer. Gene Ther 22, 297–304 (2015). https://doi.org/10.1038/gt.2014.123

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