Histone deacetylase inhibitor trichostatin a enhances the antitumor effect of the oncolytic adenovirus H101 on esophageal squamous cell carcinoma in vitro and in vivo

Abstract

Replication-selective oncolytic virotherapy provides a novel modality to treat cancer by inducing cell death in tumor cells but not in normal cells. However, the utilization of oncolytic viruses as a stand-alone treatment is problematic due to their poor transduction efficiency in vivo. H101 was the first oncolytic adenovirus (Ads) to be approved by the Chinese FDA, and exhibits modest antitumor effects when applied as a single agent. The multiple histone deacetylase inhibitor trichostatin A (TSA) has been demonstrated to potently enhance the spread and replication of oncolytic Ads in several infection-resistant types of cancer. The present study aimed to investigate the antitumor effects of H101 in combination with TSA on esophageal squamous cell carcinoma (ESCC) in vitro and in vivo, and determine the mechanisms underlying these effects. H101 and TSA in combination increased the survival of mice harboring human ESCC cell line-tumor xenografts, as compared with mice treated with these agents individually. Therefore, TSA may enhance the antitumor effects of H101 in ESCC.