OBJECTIVE: To evaluate the effects of dutasteride on the expression of angiogenesis markers in rat and human prostates. MATERIAL AND METHODS: Eight-week-old male Sprague-Dawley rats were divided into three groups of six each according to dutasteride dose, including the control group (regular diet), 2.5 mg group (2.5 mg/kg dutasteride) and 5.0 mg group (5.0 mg/kg dutasteride). A total of 41 patients awaiting transurethral resection of the prostate (TURP) were divided into two groups: 20 patients received no medication and 21 received 0.5 mg dutasteride daily for 2-4 weeks until TURP. RESULTS: At 2 weeks, dutasteride effected a significant decrease in body weight and prostate weight compared with the control rat group. Analysis by reverse transcription-polymerase chain reaction and Western blot revealed that hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) expression was lower in the dutasteride-treated groups than in the control group, except for HIF-1alpha protein. HIF-1alpha and VEGF expression was similar in the 2.5 mg and 5.0 mg groups. Human prostate tissues demonstrated homogeneous staining of HIF-1alpha and VEGF with regard to extent, intensity and intracellular location in both groups. There was no significant difference in microvessel density between the two groups. CONCLUSIONS: The expression of HIF-1alpha and VEGF in rat prostates is suppressed by dutasteride. However, less than 4 weeks of dutasteride administration does not suppress the expression of HIF-1alpha, VEGF and microvessel density in human prostate tissue. Further clinical investigation with dutasteride including a larger, placebo-controlled study is warranted to establish the mechanism and duration of dutasteride.
OBJECTIVE: To evaluate the effects of dutasteride on the expression of angiogenesis markers in rat and human prostates. MATERIAL AND METHODS: Eight-week-old male Sprague-Dawley rats were divided into three groups of six each according to dutasteride dose, including the control group (regular diet), 2.5 mg group (2.5 mg/kg dutasteride) and 5.0 mg group (5.0 mg/kg dutasteride). A total of 41 patients awaiting transurethral resection of the prostate (TURP) were divided into two groups: 20 patients received no medication and 21 received 0.5 mg dutasteride daily for 2-4 weeks until TURP. RESULTS: At 2 weeks, dutasteride effected a significant decrease in body weight and prostate weight compared with the control rat group. Analysis by reverse transcription-polymerase chain reaction and Western blot revealed that hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) expression was lower in the dutasteride-treated groups than in the control group, except for HIF-1alpha protein. HIF-1alpha and VEGF expression was similar in the 2.5 mg and 5.0 mg groups. Human prostate tissues demonstrated homogeneous staining of HIF-1alpha and VEGF with regard to extent, intensity and intracellular location in both groups. There was no significant difference in microvessel density between the two groups. CONCLUSIONS: The expression of HIF-1alpha and VEGF in rat prostates is suppressed by dutasteride. However, less than 4 weeks of dutasteride administration does not suppress the expression of HIF-1alpha, VEGF and microvessel density in human prostate tissue. Further clinical investigation with dutasteride including a larger, placebo-controlled study is warranted to establish the mechanism and duration of dutasteride.
Authors: Alexander B Opoku-Acheampong; Dave Unis; Jamie N Henningson; Amanda P Beck; Brian L Lindshield Journal: PLoS One Date: 2013-10-18 Impact factor: 3.240