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Enhancing therapeutic efficacy of oncolytic vaccinia virus armed with Beclin-1, an autophagic Gene in leukemia and myeloma

Authors :
Wen Lei
Shibing Wang
Nengwen Xu
Yu Chen
Gongqiang Wu
Aibin Zhang
Xiaomin Chen
Yin Tong
Wenbin Qian
Source :
Biomedicine & Pharmacotherapy, Vol 125, Iss , Pp 110030- (2020)
Publication Year :
2020
Publisher :
Elsevier, 2020.

Abstract

Different strategies were taken to make virotherapy more effective at killing cancer cells. Among them, oncolytic virus which arms the therapeutic gene to enhance antitumor activity is a prevalent approach. In this study, a newly developed oncolytic vaccinia virus (OVV) that expresses Beclin-1 (OVV-BECN1) was tested for its in vitro and in vivo oncolytic activity in blood cancer. Results showed that the OVV exhibited higher infectivity for leukemia cells. OVV-BECN1 induced significant apoptosis-independent cell death either in wild-type leukemia and multiple myeloma (MM) cell lines or caspase-3 shRNA leukemia cell lines, and had a superior antitumor activity compared to the parent OVV. Autophagic cell death induced by OVV-BECN1 was demonstrated in vitro and in vivo experiments. Finally, upregulation of SIRT-1, a member of class III histone deacetylases, by OVV-BECN1 resulted in the deacetylation of LC3 and its distribution from the nucleus toward the cytoplasm, which might contribute to induction of autophagy. Overall, our data showed a favorable therapeutic effect of the oncolytic vaccinia virus on blood cancers through oncolytic and autophagic mechanisms, and may therefore constitute a promising and effective therapeutic strategy for treating human leukemia and MM. However, further studies are warranted for its reliable clinical translation.

Details

Language :
English
ISSN :
07533322
Volume :
125
Issue :
110030-
Database :
Directory of Open Access Journals
Journal :
Biomedicine & Pharmacotherapy
Publication Type :
Academic Journal
Accession number :
edsdoj.7a94ffc4c82945e8a07085bb9ae11f73
Document Type :
article
Full Text :
https://doi.org/10.1016/j.biopha.2020.110030