3-Phosphoinositide-dependent protein kinase-1/Akt signalling and inhibition in a canine prostate carcinoma cell line |
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| Authors: | F J Alvarez S Murahari C G Couto T J Rosol S K Kulp C-S Chen W C Kisseberth |
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| Institution: | Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA; Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA; Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH, USA |
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| 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‐3β 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. |
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| Keywords: | celecoxib cyclooxygenase-2 dog model OSU-03012 prostate cancer |
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