The JAK2/STAT5 signaling pathway as a potential therapeutic target in canine mastocytoma.
Vet Comp Oncol
; 16(1): 55-68, 2018 Mar.
Article
em En
| MEDLINE
| ID: mdl-28397975
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 ANDMETHODS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Mastocitoma
/
Doenças do Cão
/
Fator de Transcrição STAT5
/
Janus Quinase 2
Limite:
Animals
Idioma:
En
Revista:
Vet Comp Oncol
Assunto da revista:
MEDICINA VETERINARIA
/
NEOPLASIAS
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Áustria