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

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.

A Recombinant Oncolytic Pseudorabies Virus Expressing Interleukin-18, Interferon-Gamma and PH20 Genes Promotes Systemic Antitumor Immunity

“…Presently, research regarding oncolytic viruses employing PRV as a vector is relatively scarce, with studies primarily conducting in vitro and in vivo tests using a virulence-gene-knockout PRV [ 5 , 7 , 18 ]. In this study, we used PRV as an oncolytic virus vector and carried out genetic engineering to construct PRV recombinant viruses carrying anti-tumor genes for the first time and verified their therapeutic effect on the mouse pancreatic cancer tumor model.…”

“…Previous research has demonstrated that PRV-IE180 has the capacity to eliminate various types of tumor cells in vitro [ 10 ]. In addition, PRV with deleted TK , gE and gI virulence genes has been reported to possess the ability to impede tumor growth and prolong the survival time of mice in bladder cancer and colon cancer models, while simultaneously considering the efficacy and safety of oncolysis [ 5 , 19 ]. Our study also showed that the PRV with the TK , gG , gE and gI virulence genes deleted was effective in killing four tumor cell lines, including Pan02, EMT-6, CT26 and H446, thereby expanding the oncolytic spectrum of PRV in vitro.…”

“…These findings indicated that PRV-attenuated viral strains possess significant anti-tumor potential as a recombinant tumor oncolytic vector. However, the safety of oncolytic viruses is of greater concern to many researchers, and it is of concern that PRV can infect both human cancer cells and epithelial cells [ 5 ], which may pose a risk if used in human tumor therapy. In future studies, we will carry out animal toxicity experiments to evaluate the safety of PRV recombinant virus and continue to optimize the treatment dosage and treatment time interval of oncolytic virus, so as to achieve the maximum treatment effect with minimum toxic and side effects.…”

“…Oncolytic viruses (OVs) refer to a group of viruses that have either been genetically modified or occur naturally, with the ability to specifically target, infect, and destroy cancer cells while having minimal or no impact on healthy cells [ 1 ]. Viruses in the Alphaherpesvirus subfamily, such as herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), and bovine herpesvirus-1 (BHV-1), have been extensively studied due to their potential to treat tumors [ 2 , 3 , 4 , 5 ]. In 2015, the US Food and Drug Administration (FDA) approved an HSV-1 developed by BioVex for the treatment of melanoma.…”

“…As a promising gene carrier for the treatment of cancer, PRV has various advantages. Firstly, PRV has a large genome and deletes virulence genes, including TK , PK , gG , gD , gI and gE , replacing them with exogenous genes that do not affect its replication and transmission [ 4 , 5 , 7 ]. In addition, PRV vaccine strains have been used for decades and have been demonstrated with a high level of safety and efficacy in animals [ 7 ].…”