TK gene combined with mIL-2 and mGM-CSF genes in treatment of gastric cancer

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:saraxian
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AIM:Cancer gene therapy has received more and moreattentions in the recent decade.Various systems of genetherapy for cancer have been developed.One of the mostpromising choices is the suicide gene.The product ofthymidine kinase(TK)gene can convert ganciclovir(GCV)to phosphorylated GCV,which inhibits the synthesis of cellDNA,and then induces the cells to death.Cytokines play animportant role in anti-tumor immunity.This experiment wasdesigned to combine the TK gene and mIL-2/mGM-CSFgenes to treat gastric cancer,and was expected to producea marked anti-tumor effect.METHODS:TK gene was constructed into the retroviralvector pLxSN,and the mIL-2 and mGM-CSF genes wereinserted into the eukaryotic expressing vector pIRES.Thegastric cancer cells were transfected by retroviral serum thatwas harvested from the package cells.In vitro study,thetransfected gastric cancer cells were maintained in the GCV-contained medium,to assay the cell killing effect andbystander effect.In vivo experiment,retroviral serum andcytokines plasmid were transfected into tumor-bearing mice,to observe the changes of tumor volumes and survival ofthe mice.RESULTS:In vitro experiment,20 % TK gene transducedcells could cause 70-80 % of total cells to death.In vivoresults showed that there was no treatment effect in controlgroup and TK/GCV could inhibit the tumor growth.Thestrongest anti-tumor effect was shown in TK+mIL-2+mGM-CSF group.The pathologic examination showed necrosis ofthe cancer in the treated groups.CONCLUSION:TK/GCV can kill tumor cells and inhibit thetumor growth in vivo.IL-2 and GM-CSF strongly enhancethe anti-tumor effect.Through the retrovirus and liposomemethods,the suicide gene and cytokine genes are allexpressed in the tissues. AIM: Cancer gene therapy has received more and more details in the recent decade. Verious systems of genetherapy for cancer have been developed. One of the most protomyotic choices is the suicide gene. The product of thymidine kinase (TK) gene can convert ganciclovir (GCV) to phosphorylated GCV, which inhibits the synthesis of cell DNA, and then induces the cells to death. Cytokines play animportant role in anti-tumor immunity. This experiment was designed to combine the TK gene and mIL-2 / mGM-CSF genes to treat gastric cancer, and was expected to producea marked anti-tumor effect. METHODS: TK gene was constructed into the retroviral vector pLxSN, and the mIL-2 and mGM-CSF genes were inserted into the eukaryotic expressing vector pIRES.Thegastric cancer cells were transfected by retroviral serum thatwas harvested from the package cells.In vitro study, thetransfected gastric cancer cells were maintained in the GCV-contained medium, to assay the cell killing effect andbystander effect.In vivo experiment, retrovira l serum andcytokines plasmid were transfected into tumor-bearing mice, to observe the changes of tumor volumes and survival of the mice .RESULTS: In vitro experiments, 20% TK gene transducedcells could cause 70-80% of total cells to death. that there was no treatment effect in controlgroup and TK / GCV could inhibit the tumor growth.Thestrongest anti-tumor effect was shown in TK + mIL-2 + mGM-CSF group.The pathologic examination showed necrosis of the cancer in the treated groups .CONCLUSION : TK / GCV can kill tumor cells and inhibit the tumor growth in vivo. IL-2 and GM-CSF strongly enhance the anti-tumor effect. Through the retrovirus and liposome methods, the suicide gene and cytokine genes are allexpressed in the tissues.
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