The JAK2/STAT5 signaling pathway as a potential therapeutic target in canine mastocytoma.

Abstract

BACKGROUND:

Mastocytoma are frequently diagnosed cutaneous neoplasms in dogs. In non-resectable mastocytoma patients, novel targeted drugs are often applied. The transcription factor STAT5 has been implicated in the survival of human neoplastic mast cells (MC). Our study evaluated the JAK2/STAT5 pathway as a novel target in canine mastocytoma.

MATERIALS AND METHODS:

We employed inhibitors of JAK2 (R763, TG101348, AZD1480, ruxolitinib) and STAT5 (pimozide, piceatannol) and evaluated their effects on 2 mastocytoma cell lines, C2 and NI-1.

RESULTS:

Activated JAK2 and STAT5 were detected in both cell lines. The drugs applied were found to inhibit proliferation and survival in these cells with the following rank-order of potency: R763 > TG101348 > AZD1480 > pimozide > ruxolitinib > piceatannol. Moreover, synergistic anti-neoplastic effects were obtained by combining pimozide with KIT-targeting drugs (toceranib, masitinib, nilotinib, midostaurin) in NI-1 cells.

CONCLUSION:

The JAK2/STAT5 pathway is a novel potential target of therapy in canine mastocytoma.

• Authors: Alexandra Keller, Bettina Wingelhofer, Barbara Peter, Karin Bauer, Daniela Berger, Susanne Gamperl, Martin Reifinger, Sabine Cerny-Reiterer, Richard Moriggl, Michael Willmann, Peter Valent, Emir Hadzijusufovic
• Journal: Veterinary and comparative oncology (Vet Comp Oncol) Vol. 16 Issue 1 Pg. 55-68 (Mar 2018) ISSN: 1476-5829 [Electronic] England
• PMID: 28397975 (Publication Type: Journal Article)
• Copyright: © 2017 John Wiley & Sons Ltd.

Chemical References

• AZD 1480
• MSC1992371A
• Nitriles
• Norbornanes
• Pyrazoles
• Pyrimidines
• Pyrrolidines
• STAT5 Transcription Factor
• Stilbenes
• Sulfonamides
• Pimozide
• 3,3',4,5'-tetrahydroxystilbene
• fedratinib
• ruxolitinib
• Janus Kinase 2

Topics

• Animals
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dog Diseases (drug therapy, metabolism)
• Dogs
• Flow Cytometry (veterinary)
• Janus Kinase 2 (antagonists & inhibitors, metabolism)
• Mastocytoma (drug therapy, metabolism, veterinary)
• Nitriles
• Norbornanes (pharmacology)
• Pimozide (pharmacology)
• Pyrazoles (pharmacology)
• Pyrimidines (pharmacology)
• Pyrrolidines (pharmacology)
• STAT5 Transcription Factor (antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects)
• Stilbenes (pharmacology)
• Sulfonamides (pharmacology)