Effect of STEAP1 knockdown in LNCaP cells subjected to bicalutamide or docetaxel treatment

• Autor(a) principal: Cardoso, Ana Margarida Teixeira
• Data de Publicação: 2020
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/10532
• topic: Bicalutamida; Biomarcador; Cancro da Próstata; Docetaxel; Steap1; Domínio/Área Científica::Engenharia e Tecnologia::Bioquímica

PCa is the most diagnosed cancer and the second leading cause of cancer-related death in men in the western world. Delineation of pathogenetic pathways and key driver molecular alterations involved in PCa development has provided a roadmap for the evaluation of biomarkers for their potential role in predicting disease outcome and as therapeutic targets. Two of the most used drugs for the treatment of prostate cancer are bicalutamide and docetaxel. Both drugs have their limitations and some time after treatment the patient gains resistance to therapy. To improve the diagnosis and treatment of PCa, there is an idea that some proteins can function as possible biomarkers and therapeutic goals in order to improve the conventional therapies already used. There are many proteins that are dysregulated in prostate cancer, one of which is the Six transmembrane epithelial antigen of the protate 1 (STEAP1). In normal tissues the expression of STEAP1 is practically restricted to the prostate and in cases of neoplasia it is overexpressed in the prostate. The strategic location of STEAP1 on the cell surface, low expression in normal tissues and overexpression in neoplasms mark this protein as a potential target for the diagnosis and therapy of this pathology. Thus, this study aimed to evaluate whether the sensitivity of LNCaP cells to treatment with bicalutamide and docetaxel can be improved in response to silencing of the STEAP1 gene and also to perceive the clinical significance of STEAP1 overexpression as a possible predictive biomarker in response to PCa treatment. For this, the LNCaP cells were transfected with siRNAs to silence the STEPA1 gene, and then they were stimulated with bicalutamide or docetaxel. Finally, we evaluated cell proliferation and apoptosis in response to different conditions. It was observed that there is an increase in cell proliferation and a significant decrease in apoptosis, in LNCaP cells, when STEAP1 is silenced and when there is stimulation with docetaxel or docetaxel. However, synergistic effects did not occur when the combined treatment between STEAP1 silencing and the administration of bicalutamide or docetaxel was performed. In addition, the decrease in STEAP1 expression was reversed in the presence of docetaxel, but the same is not true for bicalutamide. In summary, these preliminary results suggest that STEAP1 may be involved treatment response by bicalutamide and docetaxel. These results suggest also that STEAP1 overexpression may be used as a predictive biomarker for treatment with these anticancer drugs.