溶瘤病毒
贝肯1
癌症研究
牛痘
自噬
癌细胞
白血病
病毒学
细胞凋亡
生物
程序性细胞死亡
癌症
病毒
免疫学
基因
生物化学
遗传学
重组DNA
作者
Wen Lei,Shibing Wang,Naijin Xu,Yu Chen,Gongqiang Wu,Aibin Zhang,Xiaomin Chen,Tong Yin,W. Qian
标识
DOI:10.1016/j.biopha.2020.110030
摘要
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.
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