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

The Six Transmembrane Epithelial Antigen of the Prostate 1 (STEAP1) protein has been indicated as an overexpressed oncoprotein in prostate cancer (PCa), associated with tumor progression and aggressiveness. Taxane-based antineoplastic drugs such as paclitaxel, docetaxel, or cabazitaxel, have been investigated in PCa treatment, namely for the development of combined therapies with the improvement of therapeutic effectiveness. This study aimed to evaluate the expression of STEAP1 in response to taxane-based drugs and assess whether the sensitivity of PCa cells to treatment with paclitaxel, docetaxel, or cabazitaxel may change when the STEAP1 gene is silenced. Thus, wild-type and STEAP1 knockdown LNCaP and C4-2B cells were exposed to paclitaxel, docetaxel or cabazitaxel, and STEAP1 expression, cell viability, and survival pathways were evaluated. The results obtained showed that STEAP1 knockdown or taxane-based drugs treatment significantly reduced the viability and survival of PCa cells. Relatively to the expression of proliferation markers and apoptosis regulators, LNCaP cells showed a reduced proliferation, whereas apoptosis was increased. However, the effect of paclitaxel, docetaxel, or cabazitaxel treatment was reversed when combined with STEAP1 knockdown. Besides, these chemotherapeutic drugs may stimulate the cell growth of PCa cells knocked down for STEAP1. In conclusion, this study demonstrated that STEAP1 expression levels might influence the response of PCa cells to chemotherapeutics drugs, indicating that the use of paclitaxel, docetaxel, or cabazitaxel may lead to harmful effects in PCa cells with decreased expression of STEAP1.

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

Anti­androgen drugs are the standard pharmacological therapies for treatment of non­metastatic prostate cancer (PCa). However, the response of PCa cells may depend on the anti­androgen used and often patients become resistant to treatment. Thus, studying how the anti­androgen 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 anti­androgens in regulating STEAP1 expression and investigate whether silencing STEAP1 can make PCa cells more sensitive to anti­androgen drugs. For this purpose, wild­type 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 wild­type and LNCaP­STEAP1 knockdown cells, except for c­myc expression levels, where a cumulative effect between anti­androgen treatment and STEAP1 knockdown was observed. The effect of STEAP1 knockdown alone or combined with anti­androgens in c­myc levels is required to be addressed in future studies.

O insight em psiquiatria / Insight in psychiatry

O sinal de que algo está a acontecer contribui para que o paciente reconheça que alguma coisa de estranho se está a passar consigo. Este reconhecimento faz com que o sujeito possa desempenhar uma função activa e seja um elemento colaborante do seu processo de recuperação. Cada doença apresenta, contudo, diferentes sintomas, uma vez que cada doença psiquiátrica consiste em diferentes perturbações com diversos efeitos sobre o funcionamento mental. Desta maneira, o fenómeno do insight que é registado em cada doença é diferente e expressa-se sob diferentes formas, não somente devido às manifestações clínicas da doença mas também devido às características individuais do sujeito.

The sign that something is happening contribute for the patient recognize something strange is happening with him. The recognize do that the subject may perform a active function and be a collaborate element of their recovery process. Each disease presents, however, different symptoms, once that each psychiatric illness consists in different disorders with several effects under the mental function. This way, the insight phenomenon recorded in each illness is different and expressed under different ways, not only do to clinical manifestations of the illness but also to the subject individual characteristics.

O insight em psiquiatria / Insight in psychiatry

O sinal de que algo está a acontecer contribui para que o paciente reconheça que alguma coisa de estranho se está a passar consigo. Este reconhecimento faz com que o sujeito possa desempenhar uma função activa e seja um elemento colaborante do seu processo de recuperação. Cada doença apresenta, contudo, diferentes sintomas, uma vez que cada doença psiquiátrica consiste em diferentes perturbações com diversos efeitos sobre o funcionamento mental. Desta maneira, o fenómeno do insight que é registado em cada doença é diferente e expressa-se sob diferentes formas, não somente devido às manifestações clínicas da doença mas também devido às características individuais do sujeito.(AU)

The sign that something is happening contribute for the patient recognize something strange is happening with him. The recognize do that the subject may perform a active function and be a collaborate element of their recovery process. Each disease presents, however, different symptoms, once that each psychiatric illness consists in different disorders with several effects under the mental function. This way, the insight phenomenon recorded in each illness is different and expressed under different ways, not only do to clinical manifestations of the illness but also to the subject individual characteristics.(AU)