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

• Published in: International journal of molecular sciences 2023-04, Vol.24 (7), p.6643
• Main Authors: Rocha, Sandra M, Nascimento, Daniel, Coelho, Rafaella S, Cardoso, Ana Margarida, Passarinha, Luís A, Socorro, Sílvia, Maia, Cláudio J
• Format: Article
• Language: English
• Subjects: Antigens, Neoplasm - therapeutic use; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antineoplastic drugs; Apoptosis; B cells; Cancer; Cancer therapies; Cell cycle; Cell growth; Cell Line, Tumor; Cell proliferation; Cell viability; Chemotherapy; Development and progression; Docetaxel; Docetaxel - pharmacology; Docetaxel - therapeutic use; Drugs; Evaluation; Health aspects; Humans; Male; Oxidoreductases; Paclitaxel; Paclitaxel - pharmacology; Paclitaxel - therapeutic use; Prostate - pathology; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Protein expression; Proteins; Regulatory approval; Sensitivity analysis; Survival; Taxanes; Taxoids - pharmacology; Taxoids - therapeutic use
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24076643

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 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.