Silencing of Heat Shock Protein 27 Expression Accelerates Doxazosin-induced Apoptosis in Prostate Cancer Cell Line PC-3

PURPOSE: Heat shock proteins (HSPs) are highly expressed during stress responses and cellular adaptation to environmental changes. One such protein is HSP27, a 27kDa protein that prevents cell death induced by many pro-apoptotic agents. Therefore, the aim of this study was to investigate the correlation between HSP27 expression and apoptosis induced by doxazosin treatment in prostate cancer cell line PC-3. MATERIALS AND METHODS: RT-PCR, Western blotting, and immunocytochemical staining were performed to determine whether HSP27 mRNA and protein are expressed in PC-3 cells. Next, to investigate the effects of doxazosin on apoptosis and HSP27 protein expression in PC-3 cells, the cells were stained using a TUNEL kit (to detect apoptotic cells) and with HSP27 antibody (to assess HSP27 protein expression) 6, 12, 24, and 48h after treatment with 25microM doxazosin. In addition, to determine whether HSP27 mRNA interference accelerates doxazosin-induced apoptosis of PC-3, we knocked down HSP27 with siRNA and then evaluated the rate of apoptosis after doxazosin treatment. RESULTS: HSP27 mRNA and protein were expressed in PC-3 cells. Furthermore, HSP27 mRNA and protein levels increased until 12 hours after 25microM doxazosin treatment, whereas the rate of apoptosis did not increased dramatically. After 12 hours, HSP27 expression decreased and then apoptosis was accelerated. In addition, siRNA-mediated knockdown of HSP27 induce higher apoptosis rate of PC-3 cells even before 12hrs after doxazosin treatment. CONCLUSIONS: By inhibiting apoptosis, HSP27 expression might play an important role in inhibiting progression to castration-refractory prostate cancer and resistance to anti-cancer treatment.

Efficacy of Alfuzosin After Shock Wave Lithotripsy for the Treatment of Ureteral Calculi

PURPOSE: We evaluated the efficacy of alfuzosin for the treatment of ureteral calculi less than 10 mm in diameter after extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: A randomized, single-blind clinical trial was performed prospectively by one physician between June 2010 and August 2011. A total of 84 patients with ureteral calculi 5 to 10 mm in diameter were divided into two groups. Alfuzosin 10 mg (once daily) and loxoprofen sodium 68.1 mg (as needed) were prescribed to group 1 (n=41), and loxoprofen sodium 68.1 mg (as needed) only was prescribed to group 2 (n=44). The drug administration began immediately after ESWL and continued until stone expulsion was confirmed up to a maximum of 42 days after the procedure. RESULTS: Thirty-nine of 41 (95.1%) patients in group 1 and 40 of 43 (93.0%) patients in group 2 ultimately passed stones (p=0.96). The number of ESWL sessions was 1.34+/-0.65 and 1.41+/-0.85 in groups 1 and 2, respectively (p=0.33). The patients who required analgesics after ESWL were 8 (19.5%) in group 1 and 13 (30.2%) in group 2 (p=0.31). Visual analogue scale pain severity scores were 5.33+/-1.22 and 6.43+/-1.36 in groups 1 and 2, respectively (p=0.056). The time to stone expulsion in groups 1 and 2 was 9.5+/-4.8 days and 14.7+/-9.8 days, respectively (p=0.005). No significant adverse effects occurred. CONCLUSIONS: The use of alfuzosin in combination with ESWL seems to facilitate stone passage and to reduce the time of stone expulsion but does not affect the stone-free rate.