Oncolytic Vaccinia Virus Expressing Aphrocallistes vastus Lectin as a Cancer Therapeutic Agent
Oncolytic Vaccinia Virus Expressing Aphrocallistes vastus Lectin as a Cancer Therapeutic Agent
复制标题
表达 Aphrocallistes badus 凝集素的溶瘤痘苗病毒作为癌症治疗剂
DOI：
10.3390/md17060363
复制
发表时间：
2019-06-01
期刊：
影响因子：
5.4
通讯作者：
Li, Gongchu
中科院分区：
文献类型：
--
作者：
Wu, Tao;Xiang, Yulin;Li, Gongchu
凝集素具有多种生物学功能，包括杀虫、抗菌和抗肿瘤活性。本研究将编码C型凝集素--股阿弗罗卡耳草凝集素（AVL）的基因插入到溶瘤痘苗病毒载体（oncoVV）中，构建成重组病毒oncoVV AVL，并在体外对多种肿瘤细胞系显示出显著的抗增殖活性。进一步的研究表明，oncVV-AVL在癌细胞中的复制速度明显快于oncVV。细胞内信号传导元件包括NF-κB2、NIK以及ERK被确定为被oncVV-AVL改变。AVL上调病毒复制完全依赖于ERK活性。此外，体内研究表明，oncovV-AVL在结直肠癌和肝癌小鼠模型中引起显著的抗肿瘤作用。我们的研究可能为利用海洋凝集素AVL进行溶瘤病毒治疗提供一种新的途径。
Lectins display a variety of biological functions including insecticidal, antimicrobial, as well as antitumor activities. In this report, a gene encoding Aphrocallistes vastus lectin (AVL), a C-type lectin, was inserted into an oncolytic vaccinia virus vector (oncoVV) to form a recombinant virus oncoVV-AVL, which showed significant in vitro antiproliferative activity in a variety of cancer cell lines. Further investigations revealed that oncoVV-AVL replicated faster than oncoVV significantly in cancer cells. Intracellular signaling elements including NF-κB2, NIK, as well as ERK were determined to be altered by oncoVV-AVL. Virus replication upregulated by AVL was completely dependent on ERK activity. Furthermore, in vivo studies showed that oncoVV-AVL elicited significant antitumor effect in colorectal cancer and liver cancer mouse models. Our study might provide insights into a novel way of the utilization of marine lectin AVL in oncolytic viral therapies.