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

Autor:	Degui Lin, Weiquan Liu, Peiran Li, Yongle Yu, Xiaomei Zhang, Di Zhang, Yun Zhou, Gaoxiang Chen, Jigui Wang
Rok vydání:	2019
Předmět:	040301 veterinary sciences animal diseases viruses Apoptosis Breast Neoplasms Adenocarcinoma Biology Virus 0403 veterinary science Measles virus 03 medical and health sciences Dogs 0302 clinical medicine Cell Line Tumor medicine Animals Dog Diseases Distemper Virus Canine Canine Mammary Carcinoma General Veterinary Sequence Analysis RNA Canine distemper NF-kappa B 04 agricultural and veterinary sciences medicine.disease biology.organism_classification Caspase Inhibitors Hedgehog signaling pathway In vitro Oncolytic virus Oncolytic Viruses 030220 oncology & carcinogenesis Cancer research Female
Zdroj:	Veterinary and Comparative Oncology. 17:174-183
ISSN:	1476-5829 1476-5810
DOI:	10.1111/vco.12466
Popis:	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.
Databáze:	OpenAIRE
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