Anti-tumor Effects Of Anti-tumor Recombinant Adenovirus Expressing NDV HN On Osteosarcoma Cells In Vivo And In Vitro

To investigate the antitumor effects and mechanism of the dual cancer-specificrecombinant adenovirus Ad-HT in vivo and in vitro. MTT assay was used to evaluate theantitumor effects of Ad-HT on OS-732cells. AO/EB staining, DAPI staining, Annexin Vassay and Caspase assay were used to identify the antitumor pathway of Ad-HT on OS-732cells. S180solid tumor model was used to evaluate the in vivo anti-tumor effects of Ad-HT.BALB/c mice bearing S180solid tumor model was established and the model mice wereinjected introtumor with the recombinant adenoviruses. Non-radioactive cytotoxicity assaywas then used to detect the activity of NK and CTL, and the enzyme linked immunosorbentassay was used to examine the contents of IL-2, IL-4, IL-10and IFN-γ. Ad-HT suppressedOS-732cells successfully. The in vitro antitumor effects of Ad-HT depended on the treattime and the treat dose. The infection of Ad-HT resulted in the exposure ofphosphatidylserine, the shrink of nucleus, the permeation of membrane, the activation ofcaspase, the downregulation of mitochondrial membrane potentials, and the upregulation ofreactive oxygen species. Ad-HT treatment significant increased the mean survival (above30d) the animal model in comparison with the other recombinant adenoviruses. Furthermore, inthe animal experiment, the administration of Ad-HT resulted in the activation of NK/CTLand upregulation of Th1type cytokines such as IL-2and IFN-γ. Ad-HT could effectivelysuppress OS-732cells by inducing apoptosis through mitochondrial pathway, and prolongthe mean survival of the animal model. Ad-HT also activated NK, CTL and Th1typecytokines secretion.