Objective: To construct an adenoviral vector in which the fusion gene cytosine and uracil phosphoribosyl (UPP) transferase was directed by glutathione S-transferase P1 (GSTP1) promoter, and to investigate specific killing effect of the suicide gene system on cisplatin-resistant ovarian cancer cells.
Methods: Recombinant adenovirus was generated through homologous recombination in bacteria. A2780 and A2780/DDP cells were infected with Ad and then received flucytosine (5-FC) administration. The relative survival of these cells was tested. And a bystander effect was observed by mixing gene-transferred and gene-untransferred A2780/DDP cells with 5-FC.
Results: In vitro, when MOI was 100 and 5-FC was 250 micro g/ml, relative survival rate of A2780/DDP cells was only (3.6 +/- 1.0)%; that of A2780 cells was (76.5 +/- 2.8)%. Significant bystander effect was caused by CD-UPP gene and 20% gene-transferred A2780/DDP cells induced 80.3% of total cells to death.
Conclusion: Recombinant adenovirus carrying CD-UPP gene driven by GSTP1 promoter has a specific killing effect on cisplatin-resistant ovarian cancer cells.