Abstract
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 in SK-OV-3 (deleted p53 gene) cells was observed. ACN53 reduced the colony-forming ability of SK-OV-3 cells thereby supporting that 95-98% of cells are susceptible to infection by recombinant adenovirus. ACN53 inhibited the growth of 71-98% 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 β 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.
Original language | English (US) |
---|---|
Pages (from-to) | 1617-1623 |
Number of pages | 7 |
Journal | Oncogene |
Volume | 12 |
Issue number | 8 |
State | Published - 1996 |
Keywords
- Adenoviral constructs
- Gene therapy
- Tumorigenicity
- p53
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research