In vitro and in vivo adenovirus-mediated p53 and p16 tumor suppressor therapy in ovarian cancer - See The Biology Behind: M. E. Murphy, the battle between tumor suppressors: Is gene therapy using p16(INK4a) more efficacious than p53 for treatment of ovarian carcinoma? Clin. Cancer Res., 7: 1487-1489, 2001.

Purpose: The objectives of this study were to determine the effects of aden ovirus-mediated pld and p53 on growth and apoptosis in ovarian cancer cells and on survival in nude mice implanted with human ovarian cancer cells. Experimental Design: SKOV-3 ipl (p53 and pld null), 2774 (p53 and p16 mutan t), and OVCA 420 (p53 and pld wild-type) cells were used for ill vitro stud ies, SKOV-3 ipl, 2774, and Hey A8 (p53 and p16 wild-type) cells were used i n the nude mouse studies. The El-deleted adenoviruses containing p53, pld, or beta -galactosidase cDNA were transfected into the different cell types or inoculated into the nude mice after injection with ovarian cancer cells, Results: Cell counting, microtetrazolium, and anchorage-independent growth assays on transfected cells demonstrated that pld and the p16/p53 combinati on suppressed growth, whereas p53 did not (except in the anchorage-independ ent growth assay). Although cells infected with the p16/p53 combination had decreased growth compared with cells infected with either tumor suppressor alone, the difference was only statistically significant compared with p53 . pld, p53, and the p16/p53 combination all increased apoptosis in the cell s, In the nude mice, pld treatment resulted in the longest survival for all three models, although it only reached statistical significance for the 27 74 and SKOV-3 ipl groups. Conclusions: Overall, p16 demonstrated greater growth inhibition than p53 b oth in vivo and in vitro. The p16/p53 combination demonstrated a consistent trend toward increased growth suppression and apoptosis over p16 or p53 al one. Adenovirus-mediated p16 may be a viable future treatment for ovarian c ancer.