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: N Tanaka, K Araki, D Mizokami, Y Miyagawa, T Yamashita, M Tomifuji, Y Ueda, M Inoue, K Matsushita, F Nomura, H Shimada, A Shiotani
• Journal: Gene therapy (Gene Ther) Vol. 22 Issue 4 Pg. 297-304 (Apr 2015) ISSN: 1476-5462 [Electronic] England
• PMID: 25588744 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FARP2 protein, human
• Guanine Nucleotide Exchange Factors
• MYC protein, human
• Proto-Oncogene Proteins c-myc

Topics

• Animals
• Cell Line
• Female
• Gene Transfer Techniques
• Genetic Therapy
• Genetic Vectors
• Guanine Nucleotide Exchange Factors (metabolism)
• Head and Neck Neoplasms (genetics, metabolism, therapy)
• Heterografts
• Humans
• Mice
• Neoplasm Transplantation
• Proto-Oncogene Proteins c-myc (metabolism)
• Sendai virus (metabolism)