Exendin-4, a glucagon-like peptide-1 receptor agonist, attenuates prostate cancer growth

  1. Toshihiko Yanase1,*
  1. 1Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
  2. 2Department of Urology, School of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
  3. 3Department of Pathology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
  1. *Corresponding Author: Toshihiko Yanase , E-mail: tyanase{at}fukuoka-u.ac.jp

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 anti-cancer effects of incretin. Here, we examined the effect of the incretin drug Exendin-4, a glucagon-like peptide-1 receptor (GLP-1R) agonist, on prostate cancer. In human prostate cancer tissue obtained from patients after radical prostatectomy, GLP-1R expression co-localized with P504S, a marker of prostate cancer. In in vitro experiments, Exendin-4 significantly decreased proliferation of the prostate cancer cell lines, LNCaP, PC3 and DU145, but not that of ALVA-41. This anti-proliferative 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 siRNA abolished the inhibitory effect of Exendin-4 on cell proliferation. Although Exendin-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, Exendin-4 attenuated in vivo prostate cancer growth induced by transplantation of LNCaP cells into athymic mice and significantly reduced tumor expression of P504S, Ki67 and phosphorylated ERK-MAPK. These data suggest that Exendin-4 attenuates prostate cancer growth through inhibition of ERK-MAPK activation.

Footnotes

  • # These authors contributed equally to this work.

  • Received July 29, 2013.
  • Accepted May 27, 2014.

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