<i>ING4</i>expressing oncolytic vaccinia virus promotes anti-tumor efficiency and synergizes with gemcitabine in pancreatic cancer

Abstract

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-<i>ING4</i>) to investigate its therapeutic efficacy alone or in combination with gemcitabine against pancreatic cancer cells <i>in vitro</i> and <i>in vivo</i>. <i>ING4</i> expression was determined via quantitative real-time polymerase chain reaction (qPCR) and western blot. The cytotoxicity of VV-<i>ING4</i> 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-<i>ING4</i> and gemcitabine was assessed using Chou-Talalay analysis <i>in vitro</i> and a BLAB/c mice model <i>in vivo</i>. We found that VV-ING4 significantly increases <i>ING4</i> expression, displayed greater cytotoxic efficiency, and induced pancreatic cancer cell apoptosis and G2/M phase arrest. Additionally, the combination of VV-<i>ING4</i> and gemcitabine synergistically effect <i>in vitro</i> and <i>in vivo</i>. Taken together, our data implicate VV-<i>ING4</i> as a conceivable pancreatic cancer therapeutic candidate alone or in combination with gemcitabine.