Zhejiang Sci-Tech University Hangzhou Gongchu Joint Institute of Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Mar Drugs. 2019 Jun 19;17(6):363. doi: 10.3390/md17060363.
Lectins display a variety of biological functions including insecticidal, antimicrobial, as well as antitumor activities. In this report, a gene encoding 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.
凝集素具有多种生物学功能，包括杀虫、抗菌和抗肿瘤活性。在本报告中，将一种编码凝集素（AVL）的基因插入溶瘤痘病毒载体（oncoVV）中，形成重组病毒 oncoVV-AVL，该病毒在多种癌细胞系中表现出显著的体外增殖抑制活性。进一步的研究表明，oncoVV-AVL 在癌细胞中的复制速度明显快于 oncoVV。确定细胞内信号转导元件包括 NF-κB2、NIK 和 ERK 被 oncoVV-AVL 改变。AVL 上调的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产生了显著的抗肿瘤作用。我们的研究可能为海洋凝集素 AVL 在溶瘤病毒治疗中的新用途提供了思路。
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