Int Neurourol J.  2021 Sep;25(3):219-228. 10.5213/inj.2142004.002.

Influence of Androgen Receptor Antagonist MDV3100 Therapy on Rats With Benign Prostatic Hyperplasia

• Yang M
• Xu Z
• Zhuang Z

• KMID: 2520872
• DOI: http://doi.org/10.5213/inj.2142004.002

Abstract

Purpose
To probe the effect and mechanism of androgen receptor antagonist MDV3100 on benign prostatic hyperplasia (BPH) of rats
Methods
BPH rat model was induced by testosterone propionate. Then antagomir-miR-21-3p or agomir-miR-21-3p was injected into rats before MDV3100 treatment. The prostate index was measured by weighing the wet weight of the rat prostate. The structural morphology of rat prostate was observed after hematoxylin & eosin staining. Immunohistochemistry was applied to evaluate the expression levels of Ki-6 and inflammatory cytokines (interleukin [IL]-6, IL-18, and tumor necrosis factor-α) in rat prostate tissues. Quantitative reverse transcription polymerase chain reaction was utilized for assessment of miR-21-3p expression, and Western blot for the performance of the phosphorylation levels of IKKα and p65.
Results
Injection of testosterone propionate caused increased prostate gland hyperplasia, heightened miR-21-3p level, and activated nuclear factor-kappa B (NF-κB) signaling pathway. Additionally, BPH was accompanied by inflammatory response, as evidenced by enhanced expressions of Ki-67 and inflammatory cytokines. MDV3100 exposure ameliorated BPH and suppressed miR-21-3p expression. Overexpression of miR-21-3p intensified BPH and inflammation level, while knockdown of miR-21-3p relieved BPH. The coeffect of miR-21-3p upregulation and MDV3100 subjection led to higher inflammatory response, elevated phosphorylation levels of IKKα and p65 than MDV3100 treatment alone.
Conclusions
Androgen receptor antagonist MDV3100 alleviates BPH and inflammatory response through miR-21-3p downregulation and NF-κB signaling pathway blockade.

Keyword

Androgen receptor antagonist; Benign prostatic hyperplasia; MiR-21-3p; MDV3100; NF-κB pathway; Ki-67