Investigative and clinical urology · 2025
Induction of apoptosis and growth inhibition by silodosin and abiraterone acetate in PC-3 human prostate cancer cells.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Hakim Lukman, Rahman Zakaria Aulia, Hidayatullah Furqan, Ng Anthony Chi-Fai
Аннотация
PURPOSE: Prostate cancer that progresses despite androgen deprivation therapy, known as metastatic castration-resistant prostate cancer (mCRPC) is notoriously difficult to treat. While abiraterone acetate (AA) is a standard therapy, repurposing drugs like silodosin, a selective α1A-adrenoceptor antagonist, offers promising potential.
MATERIALS AND METHODS: PC-3 human prostate cancer cells were treated with silodosin, AA, or their combination. Cell viability was assessed via CCK-8 assay, apoptosis by Annexin V-FITC/PI flow cytometry, and drug interaction using CompuSyn to determine combination index (CI) and dose reduction index (DRI).
RESULTS: Both silodosin and AA reduced cell viability concentration-dependently (half-maximal inhibitory concentration [IC₅₀]: 44.16 mM and 66.90 µM, respectively). Combination therapy yielded the lowest viability (18.03%±5.73%), significantly outperforming AA (41.79%±13.11%) and silodosin (45.35%±11.51%) alone. Silodosin induced greater apoptosis (80.94%±15.88%) than AA (22.93%±7.41%), while the combination further enhanced apoptosis (87.41%±12.25%). At ¼ IC₅₀ doses, the combination retained efficacy using markedly reduced concentrations-16.72 µM AA (8-fold reduction) and 11.04 mM silodosin (5-fold reduction). CI values across fractional effects remained <1, confirming synergism, with favorable DRI values indicating enhanced efficacy at lower doses.
CONCLUSIONS: Silodosin exhibits potent effects in reducing cell viability and promoting apoptosis in androgen-insensitive prostate cancer cells, comparable to AA. When combined, both agents demonstrate synergistic effects with reduced dosing requirements. These findings support further investigation of silodosin as a potential therapeutic in mCRPC.
MATERIALS AND METHODS: PC-3 human prostate cancer cells were treated with silodosin, AA, or their combination. Cell viability was assessed via CCK-8 assay, apoptosis by Annexin V-FITC/PI flow cytometry, and drug interaction using CompuSyn to determine combination index (CI) and dose reduction index (DRI).
RESULTS: Both silodosin and AA reduced cell viability concentration-dependently (half-maximal inhibitory concentration [IC₅₀]: 44.16 mM and 66.90 µM, respectively). Combination therapy yielded the lowest viability (18.03%±5.73%), significantly outperforming AA (41.79%±13.11%) and silodosin (45.35%±11.51%) alone. Silodosin induced greater apoptosis (80.94%±15.88%) than AA (22.93%±7.41%), while the combination further enhanced apoptosis (87.41%±12.25%). At ¼ IC₅₀ doses, the combination retained efficacy using markedly reduced concentrations-16.72 µM AA (8-fold reduction) and 11.04 mM silodosin (5-fold reduction). CI values across fractional effects remained <1, confirming synergism, with favorable DRI values indicating enhanced efficacy at lower doses.
CONCLUSIONS: Silodosin exhibits potent effects in reducing cell viability and promoting apoptosis in androgen-insensitive prostate cancer cells, comparable to AA. When combined, both agents demonstrate synergistic effects with reduced dosing requirements. These findings support further investigation of silodosin as a potential therapeutic in mCRPC.