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: F J Alvarez, S Murahari, C G Couto, T J Rosol, S K Kulp, C-S Chen, W C Kisseberth
• Journal: Veterinary and comparative oncology (Vet Comp Oncol) Vol. 5 Issue 1 Pg. 47-58 (Mar 2007) ISSN: 1476-5829 [Electronic] England
• PMID: 19754801 (Publication Type: Journal Article)