[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.