Affiliation:
1. Department of Urology, Uijeongbu Eulji Medical Center, Uijeongbu 11759, Republic of Korea
2. Department of Biohealth Convergence, Seoul Women’s University, Seoul 01797, Republic of Korea
3. Department of Urology, Nowon Eulji Medical Center, Seoul 01830, Republic of Korea
Abstract
Background: This study investigated how the expression of heat shock protein 27 (HSP27), cellular FLICE-like inhibitory protein (cFLIP), and clusterin (CLU) affects the progression of cancer cells and their susceptibility to doxazosin-induced apoptosis. By silencing each of these genes individually, their effect on prostate cancer cell viability after doxazosin treatment was investigated. Methods: PC-3 prostate cancer cells were cultured and then subjected to gene silencing using siRNA targeting HSP27, cFLIP, and CLU, either individually, in pairs, or all together. Cells were then treated with doxazosin at various concentrations and their viability was assessed by MTT assay. Results: The study found that silencing the CLU gene in PC-3 cells significantly reduced cell viability after treatment with 25 µM doxazosin. In addition, the dual silencing of cFLIP and CLU decreased cell viability at 10 µM doxazosin. Notably, silencing all three genes of HSP27, cFLIP, CLU was most effective and reduced cell viability even at a lower doxazosin concentration of 1 µM. Conclusions: Taken together, these findings suggest that the simultaneous silencing of HSP27, cFLIP, and CLU genes may be a potential strategy to promote apoptosis in prostate cancer cells, which could inform future research on treatments for malignant prostate cancer.
Reference44 articles.
1. Castration-resistant prostate cancer: Mechanisms, targets, and treatment;Amaral;Prostate Cancer,2012
2. Mechanisms of resistance in castration-resistant prostate cancer (CRPC);Chandrasekar;Transl. Androl. Urol.,2015
3. Novel therapeutic approaches for the treatment of castration-resistant prostate cancer;Heidegger;J. Steroid Biochem. Mol. Biol.,2013
4. Impact of α-adrenoceptor antagonists on prostate cancer development, progression and prevention;Wade;Am. J. Clin. Exp. Urol.,2019
5. Role of α- and β-adrenergic signaling in phenotypic targeting: Significance in benign and malignant urologic disease;Archer;Cell Commun. Signal.,2021