Effect of PI3K/AKT inhibitor on benign prostate hyperplasia and its mechanism: an experimental study / 中华男科学杂志

ABSTRACT

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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 histiocytes 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.</p><p><b>RESULTS</b>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 (P < 0.05 versus the BPH models) and (561 +/- 12.6) mg and 1.71 +/- 0.18 in the LY294002 100 mg group (P < 0.01 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 (P < 0.05 versus the BPH models), and 50.0% and 25.0% in the LY294002 100 mg group (P < 0.01 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 (P < 0.05 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 (P < 0.01 versus the BPH models).</p><p><b>CONCLUSION</b>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.</p>