Gene therapy of adenovirus mediated CD∷upp/5-FC directed by GSTP1 promoter in cisplatin-resistant ovarian cancer

Abstract

Purpose To evaluate the specific killing effect of the adenoviral vector in which CD∷upp genes were directed by the GSTP1 promoter on cisplatin-resistant ovarian cancer cells. Experimental design Cisplatin-sensitive (A2780) and cisplatin-resistant (AD6) ovarian cancer cells were infected with recombinant adenoviral plasmid carrying the CD∷upp gene driven by the GSTP1 promoter and followed with 5-FC administration. Results In vitro, when MOI was 100 and 5-FC was 250 μg/ml, relative survival rate of the AD6 cells was only 3.63 ± 1.01%, while under the same conditions, A2780 cells were 76.50 ± 2.81%. Significant bystander effect was caused by the CD∷upp gene and 20% of gene-transferred AD6 cells caused death to 80.3% of the total cells. Furthermore, a significant anti-tumor effect of the Ad.GST-CD∷upp/5-FC was observed in nude mice bearing tumors of AD6 cells. Conclusions These results indicated that adenovirus-mediated Ad.GST-CD∷upp/5-FC directed by GSTP1 promoter is an effective approach to overcome cisplatin-resistant ovarian cancer.