In vitro effects from atorvastatin and metformin on cell proliferation induced by dyslipidemic contexts in benign prostatic hyperplasia

Abstract

Benign prostatic hyperplasia (BPH) is characterized by uncontrolled proliferation of mainly stromal elements, arise from a conjunction of multiple physiopathogenic factors. Among them, the metabolic syndrome components are strongly correlated to the risk of suffering from BPH and its aggressiveness, although cellular mechanisms are slightly understood. This study aimed to evaluate in vitro the proliferative effect of Oxidized-LDL (OxLDL) and the possible inhibitory role of the main therapy used for metabolic syndrome in stromal cells primary cultures derived from patients with BPH.

In this sense, prostatic stromal cells from 3 patients with BPH were isolated, cultured and replicated in MCDB with 10% BFS, and thereafter frozen at -80°C for subsequent protocols. The cells were stimulated for 24 hours with OxLDL (20μM), atorvastatin (20μM and 2,5μM), metformin (10mM and 2 mM) or combination of both inhibitors, using vehicles as controls. Cell proliferation was determined by the resazurin technique and cell count.

Thus, OxLDL induced a remarkable cell proliferation increase (p<0.001), with uneven effects when treated with metformin and atorvastatin. Though atorvastatin promoted a mild inhibition on OxLDL cell proliferation, it was not statistically significant. On the contrary, the metformin anti-proliferative effects were statistically significant in both doses tested (p <0.01 vs OxLDL). The combination of metformin+atorvastatin, both at low and high doses, did not improve the anti-proliferative effect of metformin alone on cell proliferation induced by OxLDL.

These results confirm the pathogenic effect of OxLDL, the resulting molecule in dyslipidemic contexts, in abnormal prostate growth and suggest a direct beneficial metformin action on prostatic stromal proliferation of BPH, in the dyslipidemic environment of metabolic syndrome.