Enhancement of antitumor activity of herpes simplex virus gamma(1)34.5-deficient mutant for oral squamous cell carcinoma cells by hexamethylene bisacetamide

Cancer Gene Therapy
S NaitoY Yura

Abstract

Current oncolytic viruses exert only limited antitumor activity on their own. There is a need to increase their oncolytic capability. We evaluated the effect of a differentiating reagent, hexamethylene bisacetamide (HMBA), on the antitumor activity of a gamma(1)34.5-deficient herpes simplex virus type 1 (HSV-1) R849 for human oral squamous cell carcinoma (SCC) cells. Hexamethylene bisacetamide increased the viral yield, especially at a low input multiplicity of infection (MOI), and the transcription of immediate early genes of HSV-1. Hexamethylene bisacetamide treatment promoted the cytopathic effect of R849 and increased the proportion of dead cells. Hexamethylene bisacetamide produced more apoptotic cells in R849-infected cells as compared with parental HSV-1(F)-infected cells. The growth of oral SCC xenografts in nude mice was markedly suppressed by treatment with R849 in combination with HMBA, and the survival of the co-treated animals was significantly prolonged as compared with that of animals treated with R849 only. Herpes simplex virus type 1 mRNA was expressed in tumors and trigeminal neurons, but not in brain, lung, liver, and kidney. These results indicate that HMBA enhances the antitumor activity of R849 through the...Continue Reading

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Citations

Sep 24, 2011·Virology Journal·Motoko ShintaniYoshiaki Yura
Apr 1, 2009·Head & Neck Oncology·Edward J Shillitoe
Jun 21, 2017·Proceedings of the National Academy of Sciences of the United States of America·Ranran WangJianxin You
Sep 4, 2019·Cancer Gene Therapy·Shinichi EsakiHiroshi Kimura
Oct 1, 2020·International Journal of Molecular Sciences·Masakazu Hamada, Yoshiaki Yura

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