Melatonin Synergizes with Sorafenib to Suppress Pancreatic Cancer via Melatonin Receptor and PDGFR-ß/STAT3 Pathway.
Cell Physiol Biochem
; 47(5): 1751-1768, 2018.
Article
en En
| MEDLINE
| ID: mdl-29953970
ABSTRACT
BACKGROUND/AIMS:
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumors with poor prognosis. Conventional chemotherapies including gemcitabine have failed owing to weak response and side effects. Hence novel treatment regimens are urgently needed to improve the therapeutic efficacy. In this study, we aimed to assess the anticancer activity of melatonin and sorafenib as a novel therapy against PDAC.METHODS:
We used various apoptosis assay and PDAC xenograft model to assess anticancer effect in vitro and in vivo. We applied phospho-receptor tyrosine kinase (RTK) array and phospho-tyrosine kinase array to explore the mechanism of the combined therapy. Western blotting, proximity ligation assay, and immunoprecipitation assay were also performed for validation.RESULTS:
Melatonin synergized with sorafenib to suppress the growth of PDAC both in vitro and in vivo. The effect was due to increased apoptosis rate of PDAC cells that was accompanied by mitochondria dysfunction. The enhanced anticancer efficacy by the co-treatment could be explained by blockade of PDGFR-ß/STAT3 signaling pathway and melatonin receptor (MT)-mediated STAT3.CONCLUSIONS:
Melatonin reinforces the anticancer activity of sorafenib by downregulation of PDGFR-ß/STAT3 signaling pathway and melatonin receptor (MT)-mediated STAT3. The combination of the two agents might be a potential therapeutic strategy for treating PDAC.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
/
Compuestos de Fenilurea
/
Transducción de Señal
/
Niacinamida
/
Receptor alfa de Factor de Crecimiento Derivado de Plaquetas
/
Receptores de Melatonina
/
Factor de Transcripción STAT3
/
Melatonina
/
Proteínas de Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cell Physiol Biochem
Asunto de la revista:
BIOQUIMICA
/
FARMACOLOGIA
Año:
2018
Tipo del documento:
Article
Pais de publicación:
ALEMANHA
/
ALEMANIA
/
DE
/
DEUSTCHLAND
/
GERMANY