Expression of the glucagon-like peptide-1 receptor and its role in regulating autophagy in endometrial cancer

• Published in: BMC cancer Vol. 18; no. 1; p. 657
• Main Authors: Kanda, Ranka, Hiraike, Haruko, Wada-Hiraike, Osamu, Ichinose, Takayuki, Nagasaka, Kazunori, Sasajima, Yuko, Ryo, Eiji, Fujii, Tomoyuki, Osuga, Yutaka, Ayabe, Takuya
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 15.06.2018; BioMed Central; BMC
• Subjects: AMPK; Analysis; Apoptosis; Autophagy; Autophagy (Cytology); Autophagy - drug effects; Autophagy - physiology; Biomarkers, Tumor - analysis; Cancer; Cancer patients; Cancer therapies; Care and treatment; Cell cycle; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Development and progression; Diabetes; Endometrial cancer; Endometrial Neoplasms - mortality; Endometrial Neoplasms - pathology; Endometrium; Experiments; Female; Flow cytometry; G proteins; Glucagon; Glucagon-like peptide 1; Glucagon-like peptide-1 receptor; Glucagon-Like Peptide-1 Receptor - biosynthesis; Glucose; Health aspects; Humans; Immunofluorescence; Immunoglobulins; Immunohistochemistry; Insulin resistance; Kaplan-Meier Estimate; Kinases; Liraglutide - pharmacology; Medical prognosis; Patients; Phagocytosis; Physiology; Progesterone; Prognosis; Progression-Free Survival; Proteins; Therapeutic applications; Weight control; Western blotting; Denmark; United States > US; Japan; AMPK; Endometrial cancer; Autophagy; Progression-free survival; Glucagon-like peptide-1 receptor
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-018-4570-8

A 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. Human 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. In 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. The 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.