Five-alpha Reductase Inhibitor Influences Expression of Androgen Receptor and HOXB13 in Human Hyperplastic Prostate Tissue

Abstract

Objectives: Five-alpha reductase inhibitors (5ARIs) are known as chemopreventive agents in prostate cancer with a risk of high-grade disease. This study evaluated the effects of 5ARI on androgen receptor (AR) and proteins involved in prostate cell growth such as HOXB13 expression in human prostate tissue and LNCaP prostate cancer cells. Materials and Methods:We retrospectively selected 21 patients who underwent TURP between March 2007 and February 2010 for previously confirmed BPH by prostate biopsy. They were grouped into control (group 1, n = 9) and 5ARI treatment (group 2, n = 12) before TURP. AR and HOXB13 expression in prostate tissue was evaluated by immunohistochemical staining. We tested the effect of 5ARI on the expression of AR, prostate specific antigen (PSA) and HOXB13 in LNCaP cells. Cells were assessed by Western blot analysis, MTT in vitro proliferation assay, and ELISA. Results: Group 2 showed stronger reactivity for AR and HOXB13 than those of the group 1. MTT assay showed death of LNCaP cells at 25uM of 5ARI. At the same time, ELISA assay for PSA showed that 5ARI inhibited secretion of PSA in LNCaP cells. Western blot analysis showed that 5ARI did not greatly alter AR expression but it stimulated the expression of HOXB13. Conclusions: These results demonstrated that 5ARI influences AR and HOXB13 expression in both LNCaP cells and human prostate tissue. In order to use 5ARI in chemoprevention of prostate cancer, we still need to clarify the influence of 5ARI in ARs and oncogenic proteins and its regulation pathway. Five-alpha

Design of Liposome Formulations for CRISPR/Cas9 Enzyme Immobilization: Evaluation of 5-Alpha-Reductase Enzyme Knockout for Androgenic Disorders

“…64 However, it has been reported that long-term inhibitor use also causes upregulation of 5-alpha reductase. 65,66 Therefore, the genetic knockout of 5alpha reductase maintains its clinical potential.…”

“…Dutasteride inhibits 5α-reductases, leading to a 95% decrease in serum DHT concentrations . However, it has been reported that long-term inhibitor use also causes upregulation of 5-alpha reductase. , Therefore, the genetic knockout of 5-alpha reductase maintains its clinical potential.…”

Finasteride Use and Risk of Bladder Cancer in a Multiethnic Population

“…5,6 Five α-reductase inhibitors inhibit the production of dihydrotestosterone and downregulate AR-dependent pathways. 7,8 Clinical studies have demonstrated that androgen suppression therapy using 5ARI, or androgen deprivation therapy using androgen receptor antagonists/continuous GnRH, can reduce BCa incidence or decrease BCa recurrence after transurethral resection. 9,10…”

“…5,6 Five a-reductase inhibitors inhibit the production of dihydrotestosterone and downregulate AR-dependent pathways. 7,8 Clinical studies have demonstrated that androgen suppression therapy using 5ARI, or androgen deprivation therapy using androgen receptor antagonists/continuous GnRH, can reduce BCa incidence or decrease BCa recurrence after transurethral resection. 9,10 Specifically, in an analysis of the Prostate, Lung, Colorectal, and Ovarian cancer screening study, the authors reported that use of the selective type II 5ARI finasteride was associated with a reduced incidence of BCa (HR[0.63, 95% CI 0.49e0.82; p[0.0004).…”