Adenoviral-mediated p53 tumor suppressor gene therapy of human ovarian carcinoma

Oncogene. 1996 Apr 18;12(8):1617-23.


Mutations of p53 gene are reported in 50-60% of human cancers and reintroduction of wild-type p53 can suppress cell proliferation. In this study, replication deficient recombinant adenovirus encoding wild-type p53 (ACN53) under the control of the human cytomegalovirus (CMV) promoter was constructed. A specific incorporation of the p53 gene with ACN53 reduced 3 (deleted p53 gene) cells was observed. ACN53 reduced the colony-forming ability of SK-OV-3 cells 72-216 h after single infection. A highly aggressive ovarian xenograft model was established in which animals die between 25-45 days. A localization study with the adenovirus-containing beta galactosidase reporter gene showed effective gene transfer in the tumor tissues. Ex vivo treatment of SK-OV-3 cells with ACN53 followed by injection into nude mice, increased the survival of the p53 treated mice by more than 50% compared with control animals. Gene therapy with ACN53 in intraperitoneal model of SK-OV-3 cells in two independent experiments revealed that there were some long-term survivors in the group of mice [2/5 (66 and 120 days) and [2/8 (166 and 423 days)] treated with ACN53. These findings demonstrate the potential of the p53 tumor suppressor gene therapy in human ovarian carcinoma.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / therapy*
  • Adenocarcinoma / virology
  • Adenoviridae / genetics*
  • Animals
  • Carcinogenicity Tests
  • Female
  • Genes, p53*
  • Genetic Therapy*
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Nude
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / therapy*
  • Ovarian Neoplasms / virology
  • Transduction, Genetic
  • Tumor Cells, Cultured