title: 3-Phosphoinositide-dependent protein kinase-1/Akt signalling and inhibition in a canine prostate carcinoma cell line.
abstract: Deregulation of the 3-phosphoinositide-dependent protein kinase-1 (PDK-1)/Akt signalling pathway is associated with prostate cancer development and progression. Inhibition of PDK-1/Akt signalling can be achieved using structurally optimized celecoxib derivatives such as OSU-03012. In this study, we treated the novel canine prostate cancer cell line, Ace-1, with OSU-03012 or dimethyl sulphoxide in vitro. We found that Akt was constitutively phosphorylated in the canine prostate cancer cell line Ace-1 and that there was a dose-dependent decrease in cell viability, and Akt and glycogen synthase kinase-3beta phosphorylation, in response to OSU-03012 treatment. This was accompanied by a dose-dependent increase in apoptosis. These data suggest that Akt signalling pathway inhibition is a potential strategy for the treatment of dogs with prostate cancer and that canine prostate cancer is a relevant large animal model for evaluating Akt pathway inhibitors such as OSU-03012 for use in people.
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: F J
authors.initials: FJ
authors.lastname: Alvarez
authors.forename: S
authors.initials: S
authors.lastname: Murahari
authors.forename: C G
authors.initials: CG
authors.lastname: Couto
authors.forename: T J
authors.initials: TJ
authors.lastname: Rosol
authors.forename: S K
authors.initials: SK
authors.lastname: Kulp
authors.forename: C-S
authors.initials: CS
authors.lastname: Chen
authors.forename: W C
authors.initials: WC
authors.lastname: Kisseberth