Dual Silencing of Hsp27 and c-FLIP Enhances Doxazosin-Induced Apoptosis in PC-3 Prostate Cancer Cells. (19th June 2013)

• Record Type: Journal Article
• Authors: Kim, Sang Soo; Cho, Hee-Ju; Cho, Jeong-Man; Kang, Jung Yoon; Yang, Hyun-Won; Yoo, Tag Keun
• Other Names: Tefekli A. Academic Editor.; Tugcu V. Academic Editor.; Tunc M. Academic Editor.
• Is Part Of: TheScientificWorldjournal. Volume 2013(2013)
• Publication Date: 2013-06-19
• Subjects: Science -- Periodicals; Technology -- Periodicals; Medicine -- Periodicals; 505
• DOI: 10.1155/2013/174392
• Languages: English
• ISSNs: 2356-6140

Abstract

Abstract : We evaluated effect of dual gene silencing of Hsp27 and c-FLIP in doxazosin-induced apoptosis of PC-3 cell. After transfection using Hsp27 and c-FLIP siRNA mixture (dual silencing), doxazosin treatment was done at the concentrations of 1, 10, and 25 μ M. We checked apoptosis of PC-3 cells with and TUNEL staining. We also checked interaction between Hsp27 and C-FLIP in the process of apoptosis inhibition. Spontaneous apoptotic index was 5% under single gene silencing of Hsp27 and c-FLIP and 7% under dual silencing of Hsp27 and c-FLIP. When doxazosin treatment was added, apoptotic indices increased in a dose-dependent manner (1, 10, and 25 μ M): nonsilencing 10, 27, and 52%; Hsp27-silencing: 14, 35, and 68%; c-FLIP silencing: 21, 46, and 78%; dual silencing: 38, 76, and 92%. While c-FLIP gene expression decreased in Hsp27- silenced cells, Hsp27 gene expression showed markedly decreased pattern in the cells of c-FLIP silencing. The knockout of c-FLIP and Hsp27 genes together enhances apoptosis even under 1 μ M, rather than low concentration, of doxazosin in PC-3 cells. This finding suggests a new strategy of multiple knockout of antiapoptotic and survival factors in the treatment of late-stage prostate cancer refractory to conventional therapy.