Aromatase Inhibitor Sensitizes Prostatic Cells for 5- Alpha Reductase Inhibitor Treatment

Presenter: Andrew Chang

Research Category: Physical and LIfe Sciences
College: College of Science
Major(s): Biology
Student Type: Undergraduate
Graduation Date: 2023
Award Winner Category: Physical and Life Sciences

Benign Prostatic Hyperplasia (BPH) is the most prevalent proliferative prostate abnormality and the steroid 5_-reductase 2 (SRD5A2) is the predominant enzyme responsible for prostatic growth. Finasteride, a 5-alpha-reductase inhibitor (5ARI), is a commonly used medication against BPH that inhibits the conversion of testosterone to dihydrotestosterone (DHT). Our previous research demonstrated that patients lacking SRD5A2 expression by somatic epigenetic changes may be resistant to 5ARI therapy and have elevated levels of aromatase, which converts testosterone to estradiol. This study examined if aromatase inhibitors combined with finasteride regulate the growth of prostatic cells. Human prostate cell proliferation was measured by MTT assay. Cells were seeded in plates containing 10% Charcoal-stripped serum/RPMI 1640 medium, incubated in 5% CO2 at 37¡C, and treated with aromatase inhibitors (Exemestane and Letrozole), alone or with finasteride, for 48 hours before the MTT assay. Dose and time-dependent assays determined optimal dosage and time standards for different treatment groups. Data were analyzed by one-way ANOVA test. The proliferation of prostatic stromal cells was significantly inhibited by the administration of finasteride and adding Exemestane further inhibited cell proliferation, but Letrozole did not. To further investigate the relationship between aromatase inhibition and cell proliferation on prostatic cells we analyzed mRNA and protein levels to verify drug specificity. Our study suggests that aromatase inhibitor affects prostatic stromal cell proliferation. Understanding the role of aromatase/estrogenic signaling pathways in prostate cell proliferation may suggest alternative treatment strategies in BPH patients who are resistant to 5ARI therapy.