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Yigang Wang,1 Binrong Wang,1 Junnan Liang,2 Caixia Cui,3 Chang Ying,1 Fang Huang,4 Buyun Ma,1 Xiumei Zhou,1 Liang Chu21College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, People’s Republic of China; 2Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 3Department of Otorhinolaryngology, Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, People’s Republic of China; 4Department of Pathology, Zhejiang Provincal People’s Hospital, Hangzhou 310014, People’s Republic of ChinaBackground: Oncolytic virus can specifically replicate in and then lyse tumor cells, but seldom in normal cells. Further studies have shown the significant therapeutic effect of oncolytic virotherapy combining with other strategies, such as chemo-, radio-, and immunotherapy et al. In this study, we investigated the combinational effect of oncolytic virus ZD55-TRAIL and chemotherapy drug doxorubicin (DOX) on human laryngeal squamous cell carcinoma (LSCC).Methods: The effect of ZD55-TRAIL combined with DOX on cell growth was assessed in LSCC Hep2 cells and normal cells by MTT assay. Hochest 33342 staining was performed to observe cell morphological changes. Western blot was used to detect the expression of apoptotic activation proteins. The in vivo antitumor efficacy of combination treatment was estimated in laryngeal cancer xenograft models.Results: The combination of ZD55-TRAIL and DOX exhibited enhanced inhibitory effects on laryngocarcinoma cell growth, and had few side effects to normal cells in vitro. Chemotherapy drug increased the inducement of tumor cell apoptosis mediated by oncolytic virus. In vivo experiment confirmed that the combination treatment significantly inhibited Hep2 laryngocarcinoma xenografts growth in mice.Conclusion: The oncolytic viro-chemotherapy is a potent therapeutic approach for in vitro cytotoxicity evaluation of Hep2 cells and xenograft growth in vivo.Keywords: laryngocarcinoma, oncolytic virus, ZD55-TRAIL, doxorubicin

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. [ABSTRACT FROM AUTHOR]

Lung cancer stem cell ( LCSC) is critical in cancer initiation, progression, drug resistance and relapse. Disadvantages showed in conventional lung cancer therapy probably because of its existence. In this study, lung cancer cell line A549 cells propagated as spheroid bodies (named as A549 sphere cells) in growth factors-defined serum-free medium. A549 sphere cells displayed CSC properties, including chemo-resistance, increased proportion of G0/G1 cells, slower proliferation rate, ability of differentiation and enhanced tumour formation ability in vivo. Oncolytic adenovirus ZD55 carrying EGFP gene, ZD55- EGFP, infected A549 sphere cells and inhibited cell growth. Tumour necrosis factor-related apoptosis-inducing ligand ( TRAIL) armed oncolytic adenovirus, ZD55- TRAIL, exhibited enhanced cytotoxicity and induced A549 sphere cells apoptosis through mitochondrial pathway. Moreover, small molecules embelin, LY294002 and resveratrol improved the cytotoxicity of ZD55- TRAIL. In the A549 sphere cells xenograft models, ZD55- TRAIL significantly inhibited tumour growth and improved survival status of mice. These results suggested that gene armed oncolytic adenovirus is a potential approach for lung cancer therapy through targeting LCSCs. [ABSTRACT FROM AUTHOR]