With no effective treatments available for most pancreatic cancer patients, pancreatic cancer continues to be one of the most difficult malignancies to treat. Oncolytic virus mediated-gene therapy has exhibited ubiquitous antitumor potential. In this study, we constructed a novel oncolytic vaccinia virus harboring the inhibitor of growth family member 4 gene (VV-ING4) to investigate its therapeutic efficacy alone or in combination with gemcitabine against pancreatic cancer cells in vitro and in vivo. ING4 expression was determined via quantitative real-time polymerase chain reaction (qPCR) and western blot. The cytotoxicity of VV-ING4 was measured using a cell proliferation assay. Both flow cytometry and western blot were applied to analyze the cell cycle and apoptosis. Furthermore, the combination inhibitory effect of VV-ING4 and gemcitabine was assessed using Chou-Talalay analysis in vitro and a BLAB/c mice model in vivo. We found that VV-ING4 significantly increases ING4 expression, displayed greater cytotoxic efficiency, and induced pancreatic cancer cell apoptosis and G2/M phase arrest. Additionally, the combination of VV-ING4 and gemcitabine synergistically effect in vitro and in vivo. Taken together, our data implicate VV-ING4 as a conceivable pancreatic cancer therapeutic candidate alone or in combination with gemcitabine.
Keywords: ING4; gemcitabine; gene therapy; oncolytic vaccinia virus; pancreatic cancer.