Browsing by Author "Coelho, Rafaella Severino"
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- The role of STEAP1 in the sensitivity of C4-2B prostate cancer cells to taxane-based chemotherapyPublication . Coelho, Rafaella Severino; Baptista, Cláudio Jorge Maia; Rocha, Sandra Catarina Moreira daProstate cancer (PCa) is the third-leading cause of cancer death in men worldwide. As a precursor to PCa, prostatic intraepithelial neoplasia (PIN) lesions are defined as a preneoplastic growth of the prostate that could develop into carcinoma and metastatic disease. The Six Transmembrane Epithelial Antigen of the Prostate 1 (STEAP1) is a prostate-specific cell-surface antigen, almost exclusively expressed on the secretory epithelium of the prostate tissue. However, this protein is known to be overexpressed in several types of cancer, including PCa. The STEAP1 protein is found on cell-cell junctions and acts as an ion channel or transporter of small molecules, indicating that this protein plays an important role in cell communication. In cancer, STEAP1 overexpression has been associated with inhibition of apoptosis, enhancement of cell proliferation, migration, and invasion, as well as induction of epithelial to mesenchymal transition. Furthermore, a link between overexpression of STEAP1 and poor prognosis in PCa has also been found. The most common approach for metastatic castration-resistant PCa treatment is the sequential prescription of single-agent therapies. Among those agents are the so-called taxane-based chemotherapeutics, a category of highly useful antineoplastic drugs, which includes paclitaxel, docetaxel, and cabazitaxel. However, as the disease progresses, patients become resistant to treatment. Currently, up to 90 % of cancerrelated deaths are due to the emergence of drug resistance. Nonetheless, combined therapies have been explored in an attempt to overcome the resistance and improve the therapeutic effectiveness. This study aimed to assess the sensitivity of PCa cells to taxane-based drugs when the STEAP1 gene is silenced, as well as to evaluate the expression of STEAP1 in response to the same drugs. C4-2B cells were selected to be transfected with a specific siRNA against the STEAP1 gene or with a scramble siRNA sequence. Wild-type and STEAP1-knockdown C4-2B cells were treated with paclitaxel, docetaxel, or cabazitaxel, and STEAP1 expression and cell viability were evaluated. The results showed that STEAP1 knockdown or taxane-based treatment significantly reduced the viability of PCa cells. However, the effect was reversed when the drugs were combined with STEAP1 knockdown, where the cell viability of C4-2B cells increased. This study demonstrated that STEAP1 expression levels might influence the response of PCa cells to chemotherapeutics drugs. Moreover, it seems that the use of paclitaxel, docetaxel, or cabazitaxel is more effective in PCa cells that overexpress STEAP1.