The Effects of Oncolytic Pseudorabies Virus Vaccine Strain Inhibited the Growth of Colorectal Cancer HCT-8 Cells In Vitro and In Vivo

SIMPLE SUMMARY: Oncolytic viruses have emerged as a viable therapy for cancers, and we explored the oncolytic effects of pseudorabies virus on colorectal cancer cells. The replication capacity and cytotoxic effect of the virus were investigated on colorectal cancer cells, meanwhile, the antitumor ability and safety were evaluated in a mouse tumor transplantation model tumor transplantation. For the first time, we found that the attenuated live vaccine strain of pseudorabies virus used in this study showed better anti-tumor activity. These results set the stage for subsequent clinical trials of tumor therapy using oncolytic viruses in non-primates and humans. ABSTRACT: Oncolytic viral therapy is a promising treatment approach for a variety of tumor forms. Although a number of studies have demonstrated that the pseudorabies virus (PRV) may be applied as an oncolytic carrier, the anti-colorectal cancer impact of the virus and the mechanism of its cytotoxic effect remain elusive. In this study, the replication capacity and cell activity of PRV attenuated live vaccines Bartha K61 and HB98 in HCT-8 cells in vitro were investigated. Next, the antitumor ability and safety were evaluated in a mouse model of HCT-8 tumor transplantation. Both PRV strains were able to suppress tumor growth and HB98 showed higher safety and efficiency than the Bartha K61 strain. Finally, flow cytometry and immunohistochemistry examination were performed to investigate its possible cytotoxic mechanism. The results showed that PRV inhibited tumor proliferation both in vitro and in vivo by inducing apoptosis. In summary, our study discovered for the first time that the live attenuated PRV has an oncolytic effect on HCT-8 cells with high efficacy and safety.