Anti-tumor Study Of Oncolytic Vaccinia Virus Carrying Aphrocallistes Vastus Lectin Gene

Recently,the morbidity rate and the death rate of the cancer tend to be going up,which have been a main killer to threaten to the human life and health.New treatments are urgently required to cure the disease.Based on gene-targeted therapy,oncolytic vaccinia virus has become a hot issue in anti-cancer research because it hase the advantages of good targetability,high expression efficiency,low cost and good anti-tumor effectLectins,as a class of specific glycosyl-binding glycoproteins,preferentially recognize and bind carbohydrate complexes,can specifically recognize cell surface receptors and specifically recognize the corresponding glycosyl sequence of the diseased cells.Lectins from different sources have different functions,some can help the body resist the invasion of foreign microorganisms and harmful substances,some animal lectins can agglutinate tumor cells Therefore,the combination therapy of lectin and oncolytic vaccinia virus may have a better anti-tumor effectIn this study,we constructed an oncolytic vaccinia virus carrying Aphrocallistes vastus lectin gene for anti-tumor research.OncoVV-AVL carrying AVL gene was packaged in 293A cells by co-transfection of WR and pCB-Flag-AVL plasmid.After amplified and purified,the anti-tumor effect of virsus was tested in vitro.In order to investigate the anti-tumor effect of AVL in adenovirus and oncolytic vaccinia virus,the cytotoxicity experiments were performed The results demonstrated that the expression of AVL could kill tumor cells and promote the anti-tumor efficacy of oncolytic vaccinia virus in cancer cells.In order to investigate the underlying mechanism of the anti-tumor effect of oncoVV-AVL,the replication ability of oncoVV-AVL was tested through TCID50 method,the results showed that oncolytic vaccinia virus harboring AVL gene significantly improved the replication ability in cancer cells.In addition,AVL down-regulated NF-?B2 phosphorylation,NIK(NF-?B kinase)level and induced ERK phosphorylation.To verify ERK played a key role in oncoVV-AVL replication,tumor cells were treated with MEK-ERK inhibitor U0126,the results indicated that the oncoVV replication completely depended on ERK activation.Finally,the efficacy of oncoVV-AVL antitumor was assessed in vivo,the data demonstrated that oncoVV-AVL achieved significant therapeutic effect in vivo.Oeans cover 71 percent of the earth and are rich in marine resources,which have broad prospects for development.The anti-tumor research of oncolytic vaccinia virus harboring marine lectin AVL gene provided new evidence for the anti-tumor of oncolytic vaccinia virus.At the same time,it provided a scientific basis for the research and development of new anti-cancer drugs of oncolytic vaccinia virus,and enlarge our limited view in therapy gene.