title: Exendin-4, a GLP-1 receptor agonist, attenuates prostate cancer growth.
abstract: Recently, pleiotropic benefits of incretin therapy beyond glycemic control have been reported. Although cancer is one of the main causes of death in diabetic patients, few reports describe the anticancer effects of incretin. Here, we examined the effect of the incretin drug exendin (Ex)-4, a GLP-1 receptor (GLP-1R) agonist, on prostate cancer. In human prostate cancer tissue obtained from patients after they had undergone radical prostatectomy, GLP-1R expression colocalized with P504S, a marker of prostate cancer. In in vitro experiments, Ex-4 significantly decreased the proliferation of the prostate cancer cell lines LNCap, PC3, and DU145, but not that of ALVA-41. This antiproliferative effect depended on GLP-1R expression. In accordance with the abundant expression of GLP-1R in LNCap cells, a GLP-1R antagonist or GLP-1R knockdown with small interfering RNA abolished the inhibitory effect of Ex-4 on cell proliferation. Although Ex-4 had no effect on either androgen receptor activation or apoptosis, it decreased extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase (MAPK) phosphorylation in LNCap cells. Importantly, Ex-4 attenuated in vivo prostate cancer growth induced by transplantation of LNCap cells into athymic mice and significantly reduced the tumor expression of P504S, Ki67, and phosphorylated ERK-MAPK. These data suggest that Ex-4 attenuates prostate cancer growth through the inhibition of ERK-MAPK activation.
authors.affiliation: Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nomiyama
authors.affiliation: Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Kawanami
authors.affiliation: Department of Urology, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Irie
authors.affiliation: Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Hamaguchi
authors.affiliation: Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Terawaki
authors.affiliation: Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka, Japan.
authors.forename: Kunitaka
authors.initials: K
authors.lastname: Murase
authors.affiliation: Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tsutsumi
authors.affiliation: Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Nagaishi
authors.affiliation: Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka, Japan.
authors.forename: Makito
authors.initials: M
authors.lastname: Tanabe
authors.affiliation: Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Morinaga
authors.affiliation: Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Pathology, Faculty of Medicine, Fukuoka University, Jonan-ku, Fukuoka, Japan.
authors.forename: Makio
authors.initials: M
authors.lastname: Mizoguchi
authors.affiliation: Department of Pathology, Faculty of Medicine, Fukuoka University, Jonan-ku, Fukuoka, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nabeshima
authors.affiliation: Department of Urology, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka, Japan tyanase@fukuoka-u.ac.jp.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yanase
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010455:Peptides / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D018027:Receptors, Glucagon / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014688:Venoms / Q000494:pharmacology*
chemical_list: C000593833:GLP1R protein, human; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D000077270:Exenatide