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BACKGROUND:
Epidemiologic studies have shown that diabetes is associated with development of benign prostatic hyperplasia (BPH). However, it is uncertain whether anti-diabetic medication prevents the development of BPH. Here we show that Metformin, a first line medication for type 2 diabetes, inhibits the proliferation of benign prostatic epithelial (BPE) cells through inhibiting the expression of insulin-like growth factor 1 receptor (IGF-1R) and adjusting the cell cycle.
METHODS:
BPE cell lines BPH-1, P69 and stromal cell line 3T3 were used. Cell proliferation and cell cycle were analyzed by MTS assay and flow cytometry, respectively. The expression of IGF-1 receptor was determined by western-blot and immunocytochemistry. The level of secreting IGF-1 in culture medium was measured by ELISA.

RESULTS:
Metformin significantly inhibited the proliferation of BPH-1 and P69 cells in a dose-dependent and time-dependent manner, but without inducing apoptosis. Administration of Metformin for 24h significantly lowered the G2/M cell population by 43.24% in P69 cell, and 24.22% in BPH-1 cell. IGF-1 pretreatment (100ng/ml, 24h) not only stimulated the cell proliferation (increased by 28.81% in P69 cells and 20.95% in BPH-1 cells) but also enhanced the expression of IGF-1R. This stimulation was abrogated by Metformin. In 3T3 cells, the secretion of IGF-1 was robustly inhibited by Metformin from 574.31pg/ml to 197.61pg/ml. Metformin prevented the proliferation and IGF-1R expression of BPH-1 and P69 cells stimulated by 3T3 cell cultured medium.
CONCLUSIONS:
Metformin inhibits BPE cells by suppressing the expression of IGF-1R and regulating cell cycle. Metformin may have a protective role against prostatic proliferation and growth.