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Oncolytic activity of canine distemper virus in canine mammary tubular adenocarcinoma cells.
- Source :
-
Veterinary and comparative oncology [Vet Comp Oncol] 2019 Jun; Vol. 17 (2), pp. 174-183. Date of Electronic Publication: 2019 Mar 24. - Publication Year :
- 2019
-
Abstract
- 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 signalling 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 signalling pathway. Inhibition of the NF-κB pathway abrogated CDV-L-induced cleaved-caspase-3 and cleaved-PARP. In a CIPp subcutaneous xenograft mouse model, intratumoural injections of CDV-L significantly restricted tumour growth without apparent pathology, and virus remained localized within the tumour. Taken altogether, these findings indicate that CDV-L exerts an antitumour effect in CIPp cells, and that apoptosis and the NF-κB pathway play essential roles in this process.<br /> (© 2019 John Wiley & Sons Ltd.)
- Subjects :
- Adenocarcinoma virology
Animals
Apoptosis drug effects
Breast Neoplasms virology
Caspase Inhibitors
Dogs
Female
NF-kappa B genetics
Sequence Analysis, RNA veterinary
Adenocarcinoma veterinary
Breast Neoplasms veterinary
Cell Line, Tumor drug effects
Distemper Virus, Canine pathogenicity
Dog Diseases virology
Oncolytic Viruses pathogenicity
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5829
- Volume :
- 17
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Veterinary and comparative oncology
- Publication Type :
- Academic Journal
- Accession number :
- 30756476
- Full Text :
- https://doi.org/10.1111/vco.12466