exenatide and Brain-Neoplasms

GLP-1 analogue exendin-4, a glucagon-like peptide 1 receptor (GLP-1R) agonist which shares 53% sequence with GLP-1, plays an essential role in human tumors. However, the function and mechanisms underlying the effects of exendin-4 on glioma cell migration, invasion and epithelial-to-mesenchymal transition are still obscure. Firstly, we demonstrated that GLP-1R was expressed in all glioma cell lines including U87, U251, U373 and A172. Exendin-4 treatment inhibited glioma cell survival, proliferation, migration and invasion. Also, exendin-4 inhibited epithelial-to-mesenchymal transition through positively regulating the expression of E-cadherin (epithelial marker), and negatively regulating the level of Vimentin (mesenchymal marker). Interestingly, we next demonstrated that exendin-4 elevated sirt3 expression dependent on the high level of GLP-1R in U87 and 251 cells. Finally, we confirmed that depletion the level of GLP-1R or sirt3 both reversed the inhibitory action of exendin-4 on glioma cell migration and invasion. These findings demonstrate that exendin-4 treatment suppressed the migration and invasion of glioma cells through GLP-1R/sirt3 pathway and exendin-4 plays an inhibitory effect on glioblastoma cell migration and invasion.

Topics: Antigens, CD; Antineoplastic Agents; Brain Neoplasms; Cadherins; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Epithelial-Mesenchymal Transition; Exenatide; Gene Expression Regulation, Neoplastic; Glioma; Glucagon-Like Peptide-1 Receptor; Humans; Neoplasm Invasiveness; Peptides; Signal Transduction; Sirtuin 3; Venoms; Vimentin

Patients with hypothalamic tumors frequently experience severe obesity, and its treatment with diet, exercise, and/or pharmacologic treatment has had limited effect. Glucagon-like peptide-1 agonist exenatide (exendin-4), used for treatment of type 2 diabetes, causes persistent weight loss via signaling in the brainstem.. We report the case of a 17-year-old patient with obesity resulting from a hypothalamic germ cell tumor. He was treated by chemoradiotherapy and exenatide at a dose of 5 µg subcutaneously twice daily.. Exenatide resulted in a 29-kg weight loss (BMI reduction from 37.1 to 29.1) after 2.5 years of treatment; significant weight gain occurred shortly after exenatide was discontinued.. Exenatide resulted in considerable reduction of body weight in a patient with severe hypothalamic obesity. This novel observation requires follow-up clinical studies for establishing the effects of exenatide in patients with disrupted hypothalamic energy regulatory pathways.

Topics: Adolescent; Brain Neoplasms; Exenatide; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Hypothalamic Neoplasms; Male; Neoplasms, Germ Cell and Embryonal; Obesity; Peptides; Venoms