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Exp Clin Endocrinol Diabetes ; 125(2): 91-97, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28008585

ABSTRACT

Background: Research has shown that the incidence of prostate cancer is increased in patients with type 2 diabetes mellitus (T2DM) 1. Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone that enhances glucose-dependent insulin secretion and suppresses glucagon release. Method: Here, we examined the effect of exenatide and liraglutide, 2 types of GLP-1 analogues, on prostate cancer cells growth by CCK-8 assay, Hoechst33258 staining assay, and western blot analysis of apoptosis-related proteins Bax and Bcl-2. Also the kinase pathways maybe involved and the expression of GLP-1 receptor (GLP-1 R) in LNCap cells was detected. Results: In our experiments, exenatide and liraglutide significantly inhibited the proliferation of the LNCap cell lines and induced the cell apoptosis. Exenatide (1-100 nmol/L) increased the ratio of Bax/Bcl-2 in a dose-dependent manner, whereas liraglutide increased Bax/Bcl-2 ratio only at concentrations of 10 nmol/L. And we found that GLP-1 analogues activate p38 but not ERK1/2 or AKT in LNCap cells. And classical GLP-1 receptor was detected in LNCap cells. Conclusion: These data suggest that exenatide and liraglutide attenuate prostate cancer growth through regulating P38 pathway by binding with GLP-1R.


Subject(s)
Apoptosis/drug effects , Cell Proliferation/drug effects , Glucagon-Like Peptide 1 , Liraglutide/pharmacology , MAP Kinase Signaling System/drug effects , Peptides/pharmacology , Prostatic Neoplasms/metabolism , Venoms/pharmacology , Cell Line, Tumor , Dose-Response Relationship, Drug , Exenatide , Glucagon-Like Peptide 1/analogs & derivatives , Glucagon-Like Peptide 1/pharmacology , Humans , Male , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Prostatic Neoplasms/pathology , Proto-Oncogene Proteins c-bcl-2/metabolism , bcl-2-Associated X Protein/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
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