Adenoviral-mediated p53 tumor suppressor gene therapy of human ovarian carcinoma.
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.
Mujoo
K
K
Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston 77030, USA.
Maneval
D C
DC
Anderson
S C
SC
Gutterman
J U
JU
D000230:Adenocarcinoma / Q000235:genetics / Q000628:therapy* / Q000821:virology; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015197:Carcinogenicity Tests; D005260:Female; D016158:Genes, p53; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000235:genetics / Q000628:therapy* / Q000821:virology; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured