[Effect of PI3K/AKT inhibitor on benign prostate hyperplasia and its mechanism: an experimental study].

Objective:To explore the effect of the phosphoinositide 3-kinase/protein kinase B(PI3K/PKB or PI3K/AKT) signaling pathway inhibitor on benign prostate hyperplasia(BPH) and its mechanism.Methods:Forty-eight SD male adult rats aged 12 weeks were equally randomized to 4 groups:sham operation control,BPH model,50 mg LY294002 and 100 mg LY294002.The BPH models were made by muscular injection of testosterone propionate at 10 mg/kg/d for 30 days following castration.The LY294002 groups were treated with the PI3K/AKT signaling pathway inhibitor LY294002 at 50 and 100 mg/kg every other day for 30 days.The prostates of the rats were weighed and the structural changes of the prostatic histocytes observed under the light microscope.The expressions of Ki-67,anti-apoptotic Bcl-2 and apoptotic Bax were detected by immunohistochemistry,and the apoptosis of prostatic cells determined by terminal de-oxynucleotidyl transferase-mediated dUTP nick end labeling.Results:The prostate wet weight and prostatic index were(551±10.8) mg and 1.61±0.05 in the sham operation group,(687±13.8) mg and 2.15±0.12 in the BPH model group,(623±23.5) mg and 1.95±0.11 in the LY294002 50 mg group(P0.05 versus the BPH models) and(561±12.6) mg and 1.71±0.18 in the LY294002 100 mg group(P0.01 versus the BPH models).The expressions of apoptotic Bax and anti-apoptotic Bcl-2 were 16.7% and 16.7% in the sham operation group,16.7% and 58.3% in the BPH model group,33.3% and 33.3% in the LY294002 50 mg group(P0.05 versus the BPH models),and 50.0% and 25.0% in the LY294002 100 mg group(P0.01 versus the BPH models).The proliferative and apoptotic indexes were 14.2±6.4 and 6.5±1.8 in the epithelial and 7.6±2.6 and 2.5±0.3 in the interstitial tissue of the sham operation group,50.9±12.8 and 2.7±1.4 in the epithelial and 16.5±5.7 and 1.3±0.8 in the interstitial tissue of the BPH models,32.0±13.8 and 6.2±2.5 in the epithelial and 12.1±3.8 and 1.6±1.1 in the interstitial tissue of the LY294002 50 mg group(P0.05 versus the BPH models),and 17.8±14.7 and 7.4±3.6 in the epithelial and 9.5±3.4 and 2.2±1.3 in the interstitial tissue of the LY294002 100 mg group(P0.01 versus the BPH models).Conclusion:The increased proliferation and decreased apoptosis of prostatic cells in the BPH animal models might be involved in the development and progression of BPH.The PI3K/AKT signaling pathway plays an important role in the development of BPH,which could be inhibited by blocking the PI3K/AKT signaling pathway.