[Specific killing effects of adenovirus-mediated double suicide gene driven by KDR promoter on venous endothelial cells and gastric cancer cells in vitro].

OBJECTIVE: To study the specific killing effect of adenovirus(Ad)-mediated double suicide gene under regulation by KDR promoter on gastric cancer cells and venous endothelial cells in vitro.

METHODS: KDR-expressing MGC803 and ECV304 cells and non-KDR-expressing LS174T cells were infected by the two Ads (AdEasy-KDR-CDglyTK and AdEasy-CMV- CDglyTK), and expression of CDglyTK was detected by reverse transcriptional (RT) PCR. After treatment with 5-FC and GCV, the killing effects of the double suicide genes on various cells were evaluated.

RESULTS: The infection rate of the two resultant recombinant Ads did not differ significantly in the cells. RT-PCR demonstrated the presence of CDglyTK gene product in all the cells infected by Ad-CMV-CDglyTK and all but SL147T cells infected by Ad-KDR-CDglyTK. All the cells infected by Ad-CMV-CDglyTK and ECV304 and MGC803 cells infected Ad-KDR-CDglyTK were highly sensitive to the prodrugs. In contrast, LS174T cells infected by Ad-KDR-CDglyTK did not appear sensitive to the two prodrugs (P<0.001). In addition, the effect of the double suicide gene was much stronger than that of either of the single suicide gene (P<0.001), showing also considerable bystander effect.

CONCLUSIONS: The double suicide gene driven by KDR promoter has specific killing effect on KDR-expressing gastric tumor cells and venous endothelial cells in vitro.