Synergistic combination of histone deacetylase inhibitor suberoylanilide hydroxamic acid and oncolytic adenovirus ZD55-TRAIL as a therapy against cervical cancer

摘要

Oncolytic adenoviruses (OA) have been investigated as virotherapeutic agents for the treatment of cervical cancer and thus far results are promising. However, the cytotoxicity of the viruses requires improvement. The present study demonstrated that this can be achieved by combining ZD55-TRAIL, an OA containing the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene, with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). It was demonstrated that these agents act synergistically to kill HeLa cells by inducing G2 growth arrest and apoptosis. Notably, in a mouse xenograft model, ZD55-TRAIL/SAHA combination inhibited tumor growth. At the molecular level, it was found that upregulation of IB and the p50 and p65 subunits of nuclear factor-B induced by ZD55-TRAIL, can be abrogated by SAHA treatment. These data strongly suggested that ZD55-TRAIL/SAHA co-treatment may serve as an effective therapeutic strategy against cervical cancer.