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Abstract(s)
O cancro de próstata (CaP) é o segundo com maior incidência no homem. As terapias
farmacológicas mais utilizadas são as antineoplásicas (docetaxel ou cabazitaxel) e
antiandrogénicas (enzalutamida ou apalutamida). Atualmente, investigam-se novos
biomarcadores preditivos para deteção precoce, desenvolvimento de terapias
combinadas e avaliação da resposta a terapia. Alguns desses potenciais biomarcadores
encontram-se sobreexpressos no CaP, como por exemplo, a proteína Six
Transmembrane Epitelial Antigen of the Prostate 1 (STEAP1), que é expressa nas células
epiteliais e vários estudos indicam que a sobreexpressão da STEAP1 está associada à
progressão do CaP.
O objetivo deste trabalho foi avaliar se as células tumorais se tornam mais sensíveis ao
tratamento com cabazitaxel ou enzalutamida, quando associado ao silenciamento do
gene STEAP1, assim como avaliar se a sobreexpressão da STEAP1 pode ser utilizada
como biomarcador preditivo na resposta ao tratamento.
Foi realizada a transfecção das LNCaP com um siRNA específico para o gene STEAP1, e
como controlo as células foram transfectadas com um siRNA contendo uma sequência
aleatória. Seguidamente, as células foram tratadas com cabazitaxel ou enzalutamida de
forma a avaliar a influência da expressão da STEAP1 na viabilidade celular, proliferação
celular, apoptose celular, migração e invasão celular.
Os resultados demostraram que o silenciamento reduziu significativamente em 47% a
viabilidade no grupo STEAP1 siRNA. entretanto, o tratamento com cabazitaxel reverte a
diminuição da viabilidade. Constatamos que o grupo STEAP1+CBZ, apresentavam
menor expressão de p-c-myc.
Assim, estes resultados preliminares podem indicar que a STEAP1 pode influenciar na
resposta ao tratamento do CaP com cabazitaxel ou enzalutamida.
Prostate cancer (CaP) is the second with the highest increase in men. The most used pharmacological therapies are antineoplastic (docetaxel or cabazitaxel) and antiandrogenic (enzalutamide or apalutamide). Currently, new predictive biomarkers are being investigated for early detection, development of combined therapies and assessment of response to therapy. Some potential biomarkers are overexpressed in CaP, such as the Prostate Epithelial Transmembrane Antigen Six 1 (STEAP1) protein, which is expressed in epithelial cells, and several studies indicate that STEAP1 overexpression is associated with CaP progression. The aim of this study was to assess whether tumor cells become more sensitive to treatment with cabazitaxel or enzalutamide, when associated with STEAP1 gene silencing, as well as to assess whether STEAP1 overexpression can be used as a predictive biomarker in response to treatment. Transfection of LNCaP with a specific siRNA for the STEAP1 gene was performed, and as a control the cells were transfected with a siRNA containing a random sequence. Then, the cells were treated with cabazitaxel or enzalutamide to assess the influence of STEAP1 expression on cell viability, cell proliferation, cell apoptosis, cell migration and invasion. The results showed that silencing significantly reduced viability by 47% in the STEAP1 siRNA group. However, treatment with cabazitaxel reverses the decrease in viability. We found that the STEAP1+CBZ group had lower expression of p-c-myc. Thus, these preliminary results may indicate that STEAP1 may influence the response to CaP treatment with cabazitaxel or enzalutamide.
Prostate cancer (CaP) is the second with the highest increase in men. The most used pharmacological therapies are antineoplastic (docetaxel or cabazitaxel) and antiandrogenic (enzalutamide or apalutamide). Currently, new predictive biomarkers are being investigated for early detection, development of combined therapies and assessment of response to therapy. Some potential biomarkers are overexpressed in CaP, such as the Prostate Epithelial Transmembrane Antigen Six 1 (STEAP1) protein, which is expressed in epithelial cells, and several studies indicate that STEAP1 overexpression is associated with CaP progression. The aim of this study was to assess whether tumor cells become more sensitive to treatment with cabazitaxel or enzalutamide, when associated with STEAP1 gene silencing, as well as to assess whether STEAP1 overexpression can be used as a predictive biomarker in response to treatment. Transfection of LNCaP with a specific siRNA for the STEAP1 gene was performed, and as a control the cells were transfected with a siRNA containing a random sequence. Then, the cells were treated with cabazitaxel or enzalutamide to assess the influence of STEAP1 expression on cell viability, cell proliferation, cell apoptosis, cell migration and invasion. The results showed that silencing significantly reduced viability by 47% in the STEAP1 siRNA group. However, treatment with cabazitaxel reverses the decrease in viability. We found that the STEAP1+CBZ group had lower expression of p-c-myc. Thus, these preliminary results may indicate that STEAP1 may influence the response to CaP treatment with cabazitaxel or enzalutamide.
Description
Keywords
Cabazitaxel Cancro da Próstata Enzalutamida Lncap Steap1