Abstract
BackgroundA previous report showed that a glucagon-like peptide-1 receptor (GLP-1R) agonist (exenatide) induced apoptosis in endometrial cancer cells. However, the pathophysiological role of GLP-1R in endometrial cancer has not been fully elucidated. Here, we investigated the effects of the GLP-1R agonist liraglutide in endometrial cancer cells and examined the association between GLP-1R expression and clinicopathological characteristics in endometrial cancer patients.MethodsHuman Ishikawa endometrial cancer cells were treated with different concentrations of liraglutide. To assess the effects of liraglutide, cell viability, colony formation, flow cytometry, Western blotting, and immunofluorescence assays were performed. Autophagy induction was examined by analyzing LC3 and p62 expression and autophagosome accumulation. Moreover, using a tissue microarray, we analyzed GLP-1R expression in 154 endometrial cancer tissue samples by immunohistochemistry.ResultsIn accordance with the previous report, liraglutide inhibited Ishikawa cell growth in a dose-dependent manner. Liraglutide significantly induced autophagy, and phosphorylated AMPK expression was elevated. Immunohistochemical analysis revealed that GLP-1R expression was associated with positive estrogen receptor and progesterone receptor status, and higher GLP-1R expression was significantly correlated with better progression-free survival.ConclusionsThe use of liraglutide to target autophagy in endometrial cancer cells may be a novel potential treatment for endometrial cancer. Furthermore, higher GLP-1R expression may be associated with better prognosis in endometrial cancer patients.
Highlights
A previous report showed that a glucagon-like peptide-1 receptor (GLP-1R) agonist induced apoptosis in endometrial cancer cells
Obesity and type 2 diabetes have been found to be associated with increased endometrial cancer risk and adverse prognosis among endometrial cancer patients, suggesting that insulin resistance is involved in the development of endometrial cancer [5, 6]
Liraglutide inhibits cancer cell growth in a dose-dependent manner We first investigated whether endometrial cancer cells express GLP-1R by Western blot analysis
Summary
A previous report showed that a glucagon-like peptide-1 receptor (GLP-1R) agonist (exenatide) induced apoptosis in endometrial cancer cells. The pathophysiological role of GLP-1R in endometrial cancer has not been fully elucidated. We investigated the effects of the GLP-1R agonist liraglutide in endometrial cancer cells and examined the association between GLP-1R expression and clinicopathological characteristics in endometrial cancer patients. Endometrial cancer is one of the most common gynecologic malignancies in developed countries, and its incidence has been increasing in Japan [1, 2]. Endometrial cancer can be classified as type I or type II according to clinical and pathological characteristics [3]. Epidemiological and clinical data suggest that metformin, an anti-diabetes drug, could prevent certain cancers, including endometrial cancer. Metformin is considered to be a promising treatment modality for endometrial cancer.
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