Physapubescin B enhances the sensitivity of gastric cancer cells to trametinib by inhibiting the STAT3 signaling pathway.
Toxicol Appl Pharmacol
; 408: 115273, 2020 12 01.
Article
em En
| MEDLINE
| ID: mdl-33035574
ABSTRACT
Given the poor prognosis of unresectable advanced gastric cancer (GC), novel therapeutic strategies are needed. The mitogen-activated protein kinase (MAPK) signaling cascade, the most frequently activated pathway in GC, plays an important role in tumorigenesis and metastasis. The MAPK/extracellular signal-regulated kinase (ERK) pathway is an attractive therapeutic target for GC. In this study, trametinib, a mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor, reduced the p-ERK level and significantly increased signal transducer and activator of transcription 3 (STAT3) phosphorylation in GC cells, resulting in reduced sensitivity to trametinib. Physapubescin B (PB), a steroidal compound extracted from the plant Physalis pubescens L., inhibited the proliferation and induced the apoptosis of GC cells by suppressing STAT3 phosphorylation. The combination of PB and trametinib suppressed the STAT3 phosphorylation induced by trametinib, and synergistically suppressed gastric tumor growth in vitro and in vivo. Together, these results indicate that inhibition of both MEK and STAT3 may be effective for patients with MAPK/ERK pathway-addicted GC.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piridonas
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Pirimidinonas
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Neoplasias Gástricas
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Quinases de Proteína Quinase Ativadas por Mitógeno
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Inibidores de Proteínas Quinases
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Fator de Transcrição STAT3
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Vitanolídeos
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Antineoplásicos
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article