Activation of glucagon‐like peptide‐1 receptor inhibits tumourigenicity and metastasis of human pancreatic cancer cells via PI3K /Akt pathway

Mar 20, 2014Diabetes, obesity & metabolism

Activation of a blood sugar hormone receptor may reduce growth and spread of human pancreatic cancer cells through a key cell survival pathway

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Human pancreatic cancer tissues showed lower levels of GLP-1 receptor expression compared to adjacent tissues.

Lower or absent GLP-1 receptor expression is more common in advanced pancreatic tumors with larger sizes and lymphatic spread.
Negative GLP-1 receptor expression is linked to poorer patient prognosis.
Activation of GLP-1 receptors with liraglutide inhibited the growth and spread of pancreatic cancer cells in laboratory and mouse models.
Liraglutide reduced Akt activation in a dose-dependent manner, indicating a potential mechanism for its effects.
PI3K inhibitors exhibited similar suppressive effects on cancer cells as liraglutide, suggesting a shared pathway of action.

AI simplified

AIMS: It has been reported that glucagon-like peptide-1 (GLP-1) agents are associated with an increased risk of pancreatic cancer in patients with type 2 diabetes. Reports have indicated that GLP-1 promotes pancreatic metaplasia and premalignant lesions. The aims of this study were to determine the effects of GLP-1-based therapy on pancreatic cancer cells.

METHODS: Immunohistochemistry was used to investigate GLP-1 receptor (GLP-1R) expression in 30 human pancreatic cancer tissues. We also analysed associated clinicopathological data and each patient's prognosis. Two human pancreatic cancer cell lines were used to evaluate the in vitro effects of the GLP-1R agonist liraglutide on cell growth, migration and invasion. Mouse xenograft models of human pancreatic cancer were established to evaluate the effects of liraglutide in vivo.

RESULTS: Human pancreatic cancer tissues showed lower levels or a lack of GLP-1R expression when compared with levels in the tumour-adjacent pancreatic tissues. Negative GLP-1R expression occurred more frequently in advanced tumours with larger diameters and lymphatic metastasis, and was associated with a poor prognosis. GLP-1R activation with liraglutide inhibited tumourigenicity and metastasis of human pancreatic cancer cells in vitro and in vivo. Akt activation was dose-dependently inhibited by liraglutide, and the PI3K inhibitors, LY294002 and wortmannin, displayed similar suppressive effects to liraglutide in human pancreatic cancer cells.

CONCLUSIONS: GLP-1R activation has an antitumour effect on human pancreatic cancers via inhibition of the PI3K/Akt pathway. This finding suggests that GLP-1-based therapies may be beneficial, rather than harmful, in treating type 2 diabetic patients with pancreatic cancer.

Full Text

Full text is available at the source.

View full text ↗

Activation of glucagon‐like peptide‐1 receptor inhibits tumourigenicity and metastasis of human pancreatic cancer cells via PI3K /Akt pathway

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief