Activation of glucagon-like peptide-1 receptor inhibits growth and promotes apoptosis of human pancreatic cancer cells in a cAMP-dependent manner.
Am J Physiol Endocrinol Metab
; 306(12): E1431-41, 2014 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-24801389
ABSTRACT
Glucagon-like peptide-1 (GLP-1) promotes pancreatic ß-cell regeneration through GLP-1 receptor (GLP-1R) activation. However, whether it promotes exocrine pancreas growth and thereby increases the risk of pancreatic cancer has been a topic of debate in recent years. Clinical data and animal studies published so far have been controversial. In the present study, we report that GLP-1R activation with liraglutide inhibited growth and promoted apoptosis in human pancreatic cancer cell lines in vitro and attenuated pancreatic tumor growth in a mouse xenograft model in vivo. These effects of liraglutide were mediated through activation of cAMP production and consequent inhibition of Akt and ERK1/2 signaling pathways in a GLP-1R-dependent manner. Moreover, we examined GLP-1R expression in human pancreatic cancer tissues and found that 43.3% of tumor tissues were GLP-1R-null. In the GLP-1R-positive tumor tissues (56.7%), the level of GLP-1R was lower compared with that in tumor-adjacent normal pancreatic tissues. Furthermore, the GLP-1R-positive tumors were significantly smaller than the GLP-1R-null tumors. Our study shows for the first time that GLP-1R activation has a cytoreductive effect on human pancreatic cancer cells in vitro and in vivo, which may help address safety concerns of GLP-1-based therapies in the context of human pancreatic cancer.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Receptores de Glucagon
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AMP Cíclico
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Peptídeo 1 Semelhante ao Glucagon
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Hipoglicemiantes
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Proteínas de Neoplasias
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Antineoplásicos
Idioma:
En
Revista:
Am J Physiol Endocrinol Metab
Ano de publicação:
2014
Tipo de documento:
Article