The Study on Inhibition of Tumor Cell Proliferation by Oncolytic Adenoviruses Targeting Wnt/β-catenin Pathway and Delivering Tumor Suppressor TSLC1

Abstract: Oncolytic viruses are able to selectively infect and replicate in tumor cells， which further lyses tumor cells and produces immunological response to inhibit or kill tumor cells. Oncolytic viruses become one of the most promising fields for tumor gene therapy due to their special oncolysis and tumor targeting ability. Based on the tumor specificity of Wnt signal pathway， our study used the novel constructed oncolytic adenovirus Ad.wnt- E1A(Δ24)-TSLC1 with a mutant E1A expression cassette driven by TCF/LEF binding site promoter and delivering a tumor suppressor gene TSLC1. The Wnt signalling activity， survival rate and apoptosis of tumor cells are detected by Dual-Luciferase reporter， Western blot， MTT， crystal violet and Hoechst staining assay， respectively. The results show that tumor cells have higher Wnt signal activity and stronger sensitivity to oncolytic viruses comparing with normal cells. Ad.wnt-E1A(Δ24)-TSLC1 can effectively kill HepG2 cells and induce apoptosis through Caspase pathway activation， which provides the reference for the clinical treatment of hepatocellular carcinoma.

CSTR: 32200.14.cjcb.2017.11.0005