STEAP1 regulation and its influence modulating the response of LNCaP prostate cancer cells to bicalutamide, enzalutamide and apalutamide

Anti-androgen drugs are the standard pharmacological therapies for treatment of non-metastatic prostate cancer (PCa). However, the response of PCa cells may depend on the anti-androgen used and often patients become resistant to treatment. Thus, studying how the anti-androgen drugs affect oncogenes expression and action and the identification of the best strategy for combined therapies are essential to improve the efficacy of treatments. The Six Transmembrane Epithelial Antigen of the Prostate 1 (STEAP1) is an oncogene associated with PCa progression and aggressiveness, although its relationship with the androgen receptor signaling remains to be elucidated. The present study aimed to evaluate the effect of anti-androgens in regulating STEAP1 expression and investigate whether silencing STEAP1 can make PCa cells more sensitive to anti-androgen drugs. For this purpose, wild-type and STEAP1 knockdown LNCaP cells were exposed to bicalutamide, enzalutamide and apalutamide. Bicalutamide decreased the expression of STEAP1, but enzalutamide and apalutamide increased its expression. However, decreased cell proliferation and increased apoptosis was observed in response to all drugs. Overall, the cellular and molecular effects were similar between LNCaP wild-type and LNCaP-STEAP1 knockdown cells, except for c-myc expression levels, where a cumulative effect between anti-androgen treatment and STEAP1 knockdown was observed. The effect of STEAP1 knockdown alone or combined with anti-androgens in c-myc levels is required to be addressed in future studies.