NAD(P)H-quinone oxidoreductase 1 silencing aggravates hormone-induced prostatic hyperplasia in mice.

Abstract

NAD(P)H-quinone oxidoreductase 1 (NQO1) is a highly inducible flavoprotein known to involve in various cellular defence mechanisms. In this study, we explored whether NQO1 deletion affects hormone-induced prostatic hyperplasia. Testosterone propionate (3mg/kg, IP) was injected into wild-type (WT) and NOQ1 knockout C57BL/6 mice (NQO1-/- ) for 14 consecutive days, and the samples were collected for biological and histochemical studies. The testosterone-treated NQO1-/- showed about 140% higher prostate weight than the testosterone-treated WT, with enhanced connective tissue and hyperplastic glands formations. However, increased dihydrotestosterone level after testosterone treatment was not significantly different between the WT and NQO1-/- . In contrast, the enhanced nuclear expression of proliferating cell nuclear antigen in NQO1-/- prostate confirmed aggravated prostatic hyperplasia in NQO1-/- . Moreover, the expression of heat shock protein (HSP) 90-α was markedly increased in the NQO1-/- , and this was supported by increased testosterone-induced nuclear androgen receptor expression in NQO1-silenced LNCaP cells. Testosterone-induced prostate-specific antigen expression was not reversed in NOQ1-silenced cells after finasteride treatment. Although the exact role of NQO1 in prostatic hyperplasia remains unclear, the hyperplasia exacerbation due to NQO1 deletion might be independent of type 2 5α-reductase and might be related to enhanced androgen receptor affinity due to enhanced HSP90-α expression.