AIM:To evaluate the synergistic antitumor effects of herpessimplex virus thymidine kinase (HSV-TK) together with tumornecrosis factor alpha (TNF-α) or interleukin-2 (IL-2) geneexpression on gastric cancer cell line SGC7901.METHODS:Recombinant vectors pL(TT)SN and pL(TI)SN,which express TK-IRES-TNF-α and TK-IRES-IL-2 genesseparately,as well as the control plasmids pL(TK)SN andpLXSN were employed to transfect PA317 cells respectivelyto generate the viruses that can stably express the objectivegenes through G418 selection.The gastric cancer cells werethen transfected by the retroviral serum from the packagecells and maintained in culture to determine the cell growthand apoptosis.The cytotoxic effects of HSV-TK togetherwith TNF-α or IL-2 gene expression on the transfected cancercells were evaluated by the cell viability and bystander effectsin the presence of GCV supplemented in the cultural medium.RESULTS:Expression of recombinant proteins includingTNF-α and IL-2 by stable transfectants was confirmed byWestern blotting.The percentage of cell apoptosis in theSGC/0,SGC/TK-TNF-α,SGC/TK-IL-2 and SGC/TK clone was2.3%,12.3%,11.1% and 10.9% respectively at 24 h post-transfection.Cell growth status among all the experimentalgroups as judged by cell absorbance (A) at 570nm did notexhibit any significant difference (P>0.05);although it wasnoted to be slightly lower in the SGC/TT group.Cell survivalrate in SGC/TI,SGC/TT and SGC/TK group was significantlydecreased in a dose-dependent manner of GCV comparedwith that of the SGC/0 group (P<0.05-0.01).Among allstudied cells,the SGC/TT was shown most sensitive to GCVwith a half lethal dose of 0.5 mg.L~(-1).In contrast,the survivalrate of SGC/0 cells was not affected by the presence of GCVwith the doses less than 10 mg.L~(-1).The half lethal dose of GCV for SGC/0 cells was more than 100 mg·L~(-1).Markedbystander effect induced by SGC/TI,SGC/TT and SGC/TKcells was confirmed by the fact that 20% of these stabletransfectants could kill 50% of the co-cultured cells,in whichthe most prominent bystander effect was found in thecircumstance of SGC/TT presence.However,no significantdifference of these variables was found among SGC/TI,SGC/TT and SGC/TK cells (P>0.05).CONCLUSION:The synergistic antitumor effects producedby the co-expression of HSV-TK with TNF-α or IL-2 geneswere not present in the transfected SGC7901 cells,Themechanism underlying these phenomena was not known. AIM: To evaluate the synergistic antitumor effects of herpessimplex virus thymidine kinase (HSV-TK) together with tumornecrosis factor alpha (TNF-a) or interleukin-2 (IL-2) geneexpression on gastric cancer cell line SGC7901.METHODS: Recombinant vectors pL (TT) SN and pL (TI) SN, which express TK-IRES-TNF-α and TK-IRES-IL-2 genesseparately as well as the control plasmids pL (TK) SN and pLXSN were employed to transfect PA317 cells respectivelyto generate the viruses that can stably express the objectivegenes through G418 selection. The gastric cancer cells were transfected by the retroviral serum from the package cells and maintained in culture to determine the cell growthand apoptosis. cytotoxic effects of HSV-TK together with TNF-α or IL- 2 gene expression on the transfected cancer cells were evaluated by the cell viability and bystander effects in the presence of GCV supplemented in the cultural medium .RESULTS: Expression of recombinant proteins including TNF- [alpha] and IL-2 by stable transfectan ts was was by western blotting. The percentage of cell apoptosis in the SGC / 0, SGC / TK-TNF- [alpha], SGC / TK- IL-2 and SGC / TK clone was 2.3%, 12.3%, 11.1% and 10.9% at 24 h post-transfection. Cell growth status among all the experimental groups as judged by cell absorbance (A) at 570 nm did notexhibit any significant difference (P> 0.05); although it was beoted to be slightly lower in the SGC / TT group. Cell survival rate in SGC / TI, SGC / TT and SGC / TK group was significantly reduced in a dose-dependent manner of GCV compared with that of the SGC / 0 group (P <0.05-0.01) .Among allstudied cells, the SGC / most sensitive to GCV with a half lethal dose of 0.5 mg.L -1 .In contrast, the survival rate of SGC / 0 cells was not affected by the presence of GCVwith the dose less than 10 mg.L -1 The half lethal dose of GCV for SGC / 0 cells was more than 100 mg · L -1. Markedbystander effect induced by SGC / TI, SGC / TT and SGC / TK cells was confirmed by the fact that 20% of these stabletransfectants could ki ll 50% of the co-cultured cells, in which the most prominent bystander effect was found in the circulation of SGC / TT presence. However, no significant difference of these variables was found among SGC / TI, SGC / TT and SGC / TK cells ). CONCLUSION: The synergistic antitumor effects produced by the co-expression of HSV-TK with TNF-α or IL-2 geneswere not present in the transfected SGC7901 cells, Themechanism underlying these phenomena was not known.