title: Synergistic combination of histone deacetylase inhibitor suberoylanilide hydroxamic acid and oncolytic adenovirus ZD55-TRAIL as a therapy against cervical cancer.
abstract: 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 IκBα and the p50 and p65 subunits of nuclear factor-κB 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.
authors: Institute of Oncology, Women's Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.
authors: Xiujun
authors: X
authors: Han
authors: Xinyuan Institute of Medicine and Biotechnology, School of Life Science, Zhejiang Sci‑Tech University, Hangzhou, Zhejiang 310018, P.R. China.
authors: Shibing
authors: S
authors: Wang
authors: Institute of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors: Wenjing
authors: W
authors: Zhou
authors: Institute of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors: Ying
authors: Y
authors: Li
authors: Institute of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors: Wen
authors: W
authors: Lei
authors: Institute of Oncology, Women's Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.
authors: Weiguo
authors: W
authors: Lv
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004357:Drug Synergism; D005260:Female; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage*; D051379:Mice; D050130:Oncolytic Virotherapy; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D000077337:Vorinostat; D023041:Xenograft Model Antitumor Assays
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat