title: Synergistic growth inhibition by combination of adenovirus mediated p53 transfer and cisplatin in ovarian cancer cell lines.
abstract: OBJECTIVE
  This study was to investigate the synergistic growth inhibitory effect by combination of adenovirus mediated p53 gene transfer and cisplatin in ovarian cancer cell lines with different p53 gene mutation patterns.
  
  
  METHODS
  Three ovarian cancer cell lines, p53 deleted SKOV3, p53 mutated OVCAR-3, and PA-1 with wild-type p53 were transduced with human adenovirus vectors carrying p53 gene (Ad-p53) and treated with a sublethal concentration of cisplatin before and after Ad-p53. The cell number was counted daily for 5 days after Ad-p53 transduction. Western blotting was used to identify p53 and p21 protein expressions, and flow cytometric analysis was performed to investigate any change of DNA ploidy after Ad-p53 transfer.
  
  
  RESULTS
  Ad-p53 transduced cells successfully expressed p53 and p21 proteins after 48 hours of Ad-p53 transduction. Synergistic growth inhibition by combination of Ad-p53 and cisplatin was detected only in SKOV3 and OVCAR-3 cells, but not in PA-1 cells. In p53 deleted SKOV3 cells, cisplatin treatment after Ad-p53 showed higher growth inhibition than the treatment before Ad-p53 transduction, and reverse relationship was observed in p53 mutated OVCAR-3 cells. In SKOV3 cells, the fraction of cells at G2/M phase increased after cisplatin treatment, however, it decreased dramatically with Ad-p53 transduction.
  
  
  CONCLUSIONS
  The synergistic growth inhibition by combination of Ad-p53 and cisplatin may depend on the p53 status and the temporal sequence of cisplatin treatment, suggesting judicious selective application of this strategy in clinical trials.
authors.affiliation: Department of Obstetrics and Gynecology, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: Sang Young
authors.initials: SY
authors.lastname: Ryu
authors.forename: Kidong
authors.initials: K
authors.lastname: Kim
authors.forename: Woo Sik
authors.initials: WS
authors.lastname: Lee
authors.forename: Hee Chung
authors.initials: HC
authors.lastname: Kwon
authors.forename: Kee Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Chang Min
authors.initials: CM
authors.lastname: Kim
authors.forename: Soon-Beom
authors.initials: SB
authors.lastname: Kang