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

Abstract

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.

STEAP1 Knockdown Decreases the Sensitivity of Prostate Cancer Cells to Paclitaxel, Docetaxel and Cabazitaxel

“…However, most patients develop resistance to these drugs due to changes in the expression of oncogenes [ 33 ]. Recently, it was shown that STEAP1 did not alter the response of PCa cells to anti-androgen treatment [ 34 ]. Taking into account that there are no studies evaluating the relationship between STEAP1 and taxane-based chemotherapeutics, this study intended to explore the effect of chemotherapeutic drugs in modulating the expression of STEAP1, as well as to evaluate the role of STEAP1 in influencing the response of PCa cells to chemotherapeutic drugs.…”

Combined Therapies with Taxanes Based-Chemotherapeutic Drugs in Prostate Cancer: Novel Insights and Future Directions

“…Furthermore, it was reported that STEAP1 knockdown alone decreased the cell viability in both cell lines, as well as all taxane-based treatments when administered alone. However, the combination between STEAP1 knockdown and exposure to taxane-based therapy led to an increase in cell viability/proliferation and diminished levels of apoptosis [118]. Altough more studies are required, these data suggest that the combination of taxane-based drugs with STEAP1 knockdown may lead to PCa progression.…”

“…Although its function remains unclear, some studies have pointed out that STEAP1 is involved in metal reductase activity, and also in transport of ions such as Na + , Ca 2+ , and K + [117]. STEAP1 is highly expressed in LNCaP cells and also at significant levels in C4-2B cell line [118]. Regarding the effect of STEAP1 knockdown in LNCaP cells, reduced cell viability was observed in comparison to the control group.…”

“…The same study also evaluated the behavior of LNCaP cells knocked down for STEAP1 in response to DHT, and the result was that the effect of STEAP1 gene silencing was not reversed after exposure to DHT [119]. Recently, another study reported the effect of paclitaxel, docetaxel and cabazitaxel on STEAP1 expression in LNCaP and C4-2B cells [118]. It was observed that paclitaxel or cabazitaxel treatment increased the STEAP1 protein expression when compared with the control group, but no differences were observed in C4-2B cells [118].…”

“…Recently, another study reported the effect of paclitaxel, docetaxel and cabazitaxel on STEAP1 expression in LNCaP and C4-2B cells [118]. It was observed that paclitaxel or cabazitaxel treatment increased the STEAP1 protein expression when compared with the control group, but no differences were observed in C4-2B cells [118]. Furthermore, it was reported that STEAP1 knockdown alone decreased the cell viability in both cell lines, as well as all taxane-based treatments when administered alone.…”