1567 METFORMIN REGULATES THE PROLIFERATION OF PROSTATE EPITHELIAL CELLS INHIBITION OF INSULIN-LIKE GROWTH FACTOR 1 RECEPTOR

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research1 Apr 20121567 METFORMIN REGULATES THE PROLIFERATION OF PROSTATE EPITHELIAL CELLS INHIBITION OF INSULIN-LIKE GROWTH FACTOR 1 RECEPTOR Xingyuan Xiao, Zongwei Wang, and Aria F. Olumi Xingyuan XiaoXingyuan Xiao Boston, MA More articles by this author , Zongwei WangZongwei Wang Boston, MA More articles by this author , and Aria F. OlumiAria F. Olumi Boston, MA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1339AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Benign prostatic hyperplasia (BPH) is the most common age-related proliferative abnormality of the prostate affecting elderly men throughout the world. Epidemiologic studies suggest that diabetes significantly increases the risk of developing BPH. However, it is unclear whether anti-diabetic medications may be protective against development of BPH. Previously, we have found that stromally expressed insulin-like growth factor 1 (IGF-1) promotes benign prostatic epithelial (BPE) cell proliferation through paracrine mechanisms. Here we demonstrate that Metformin, a first line medication for treatment of type 2 diabetes inhibits the proliferation of BPE cells through affecting the cell cycle and inhibiting the IGF-1R expression. METHODS BPE cell lines BPH-1 and P69, and stromal cell line 3T3 were used. Cellular proliferation and cell cycle analyses were completed by MTS assay and FACS analyses, respectively. The expression of IGF-1 receptor was determined by western-blot and immunocytochemistry. Secretion of IGF-1 in supernatant was measured by ELISA. RESULTS Metformin (0.5-10mM, 6-48h) significantly inhibited the proliferation of BPH-1 and P69 cells in a dose-dependent and time-dependent, but without inducing apoptosis. Treatment with Metformin for 24h lowered the G2/M cell population by 43.24% in P69 cell, and 24.22% in BPH-1 cell. On the other hand, IGF-1 (100ng/ml, 24h) stimulated the cell proliferating (increased by 28.81% in P69 cells and 20.95% in BPH-1 cells) and significantly enhanced the expression of IGF-1R in BPE. Metformin (5mM) abrogated the proliferative effect of IGF-1 on BPE cells. In 3T3 cells, the secretion of IGF-1 was robustly inhibited by Metformin from 574.31pg/ml to 197.61pg/ml. Conditioned medium from 3T3 cells promoted the proliferation and the expression of IGF-1R in BPH-1 and P69 cells. Similarly, Metformin abrogated the ability of 3T3 conditioned medium to promote proliferation of BPE cells. CONCLUSIONS Our study demonstrates that Metformin inhibits the proliferation of BPE cells by suppressing the expression of IGF-1R. Metformin may have a protective role in prostatic proliferation by inhibition of IGF-1R. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e635 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Xingyuan Xiao Boston, MA More articles by this author Zongwei Wang Boston, MA More articles by this author Aria F. Olumi Boston, MA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...