Oncolytic activity of canine distemper virus in canine mammary tubular adenocarcinoma cells.

Canine distemper virus (CDV), bearing a close resemblance to measles virus, represents a promising candidate for oncolytic therapy; however, its application and underlying oncolytic mechanisms in canine mammary carcinoma cells remain to be explored. Here, we found that an attenuated canine distemper vaccine strain, CDV-L, efficiently infected and inhibited the growth of canine mammary tubular adenocarcinoma CIPp cells but not MDCK cells in vitro. Transcriptomic analysis of CDV-L-infected CIPp cells revealed substantially differentially expressed genes in apoptotic and NF-κB signaling pathways. Subsequent validations confirmed that CDV-L induced apoptosis of CIPp cells through the caspase-8 and caspase-3 pathway. Identification of phosphorylated-IκBα, phosphorylated-p65 and the nuclear translocation of p65 confirmed the activation of the NF-κB signaling pathway. Inhibition of the NF-κB pathway abrogated CDV-L-induced cleaved-caspase-3 and cleaved-PARP. In a CIPp subcutaneous xenograft mouse model, intratumoral injections of CDV-L significantly restricted tumor growth without apparent pathology, and virus remained localized within the tumor. Taken altogether, these findings indicate that CDV-L exerts an antitumor effect in CIPp cells, and that apoptosis and the NF-κB pathway play essential roles in this process. This article is protected by copyright. All rights reserved.