9-ING-41, a small-molecule glycogen synthase kinase-3 inhibitor, is active in neuroblastoma.
Anticancer Drugs
; 29(8): 717-724, 2018 09.
Article
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| MEDLINE
| ID: mdl-29846250
ABSTRACT
Advanced stage neuroblastoma is a very aggressive pediatric cancer with limited treatment options and a high mortality rate. Glycogen synthase kinase-3ß (GSK-3ß) is a potential therapeutic target in neuroblastoma. Using immunohistochemical staining, we observed positive GSK-3ß expression in 67% of human neuroblastomas (34 of 51 cases). Chemically distinct GSK-3 inhibitors (AR-A014418, TDZD-8, and 9-ING-41) suppressed the growth of neuroblastoma cells, whereas 9-ING-41, a clinically relevant small-molecule GSK-3ß inhibitor with broad-spectrum preclinical antitumor activity, being the most potent. Inhibition of GSK-3 resulted in a decreased expression of the antiapoptotic molecule XIAP and an increase in neuroblastoma cell apoptosis. Mouse xenograft studies showed that the combination of clinically relevant doses of CPT-11 and 9-ING-41 led to greater antitumor effect than was observed with either agent alone. These data support the inclusion of patients with advanced neuroblastoma in clinical studies of 9-ING-41, especially in combination with CPT-11.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Inhibidores Enzimáticos
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Glucógeno Sintasa Quinasa 3 beta
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Indoles
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Maleimidas
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Neuroblastoma
Límite:
Animals
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Female
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Humans
Idioma:
En
Año:
2018
Tipo del documento:
Article