title: Glucagon-like Peptide-1 Analogues Inhibit Proliferation and Increase Apoptosis of Human Prostate Cancer Cells in vitro.
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.
authors.affiliation: The Health Management Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: X-N
authors.initials: XN
authors.lastname: Li
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: H-M
authors.initials: HM
authors.lastname: Bu
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: X-H
authors.initials: XH
authors.lastname: Ma
authors.affiliation: Outpatient Office, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Sh
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Sh
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Y-L
authors.initials: YL
authors.lastname: Cui
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: J
authors.initials: J
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D000069450:Liraglutide / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014688:Venoms / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C000595707:BCL2 protein, human; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D014688:Venoms; D051028:bcl-2-Associated X Protein; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases