Abstract |
Despite recent therapeutic advances, malignant melanoma is an aggressive tumor in dogs and is associated with a poor outcome. Novel, targeted agents are necessary to improve survival. In this study, 6-bromoindirubin-3'-oxime (BIO), a serine/threonine kinase inhibitor with reported specificity for glycogen synthase kinase-3 beta (GSK-3β) inhibition, was evaluated in vitro in three canine melanoma cell lines (CML-10C2, UCDK9M2, and UCDK9M3) for β- catenin-mediated transcriptional activity, Axin2 gene and protein expression levels, cell proliferation, chemotoxicity, migration and invasion assays. BIO treatment of canine malignant melanoma cell lines at 5 µM for 72 h enhanced β- catenin-mediated transcriptional activity, suggesting GSK-3β inhibition, and reduced cell proliferation and migration. There were no significant effects on invasion, chemotoxicity, or apoptosis. The results suggest that serine/threonine kinases may be viable therapeutic targets for the treatment of canine malignant melanoma.
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Authors | Esther Chon, Brandi Flanagan, Lucas Campos de Sá Rodrigues, Caroline Piskun, Timothy J Stein |
Journal | Veterinary journal (London, England : 1997)
(Vet J)
Vol. 205
Issue 2
Pg. 305-12
(Aug 2015)
ISSN: 1532-2971 [Electronic] England |
PMID | 25130776
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Ltd. All rights reserved. |
Chemical References |
- 6-bromoindirubin-3'-oxime
- Antineoplastic Agents
- Indoles
- Oximes
- beta Catenin
- Glycogen Synthase Kinase 3 beta
- Glycogen Synthase Kinase 3
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Cell Movement
(drug effects)
- Cell Proliferation
(drug effects)
- Dog Diseases
(drug therapy)
- Dogs
- Gene Expression Regulation, Neoplastic
(drug effects)
- Glycogen Synthase Kinase 3
(genetics, metabolism)
- Glycogen Synthase Kinase 3 beta
- Indoles
(pharmacology)
- Melanoma
(drug therapy, veterinary)
- Oximes
(pharmacology)
- Transcription, Genetic
- beta Catenin
(genetics, metabolism)
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