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Effect of dutasteride on the expression of hypoxia-inducible factor-1α, vascular endothelial growth factor and microvessel density in rat and human prostate tissue

Cited 15 time in Web of Science Cited 16 time in Scopus
Authors

Ku, Ja Hyeon; Shin, Jung Ki; Cho, Min Chul; Myung, Jae Kyung; Paick, Jae-Seung; Moon, Kyung Chul

Issue Date
2009
Publisher
TAYLOR & FRANCIS AS
Citation
SCANDINAVIAN JOURNAL OF UROLOGY AND NEPHROLOGY; Vol.43 6; 445-453
Keywords
Dutasteridevascularityvascular endothelial growth factorhypoxia-inducible factorprostate
Abstract
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-1 alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF) expression was lower in the dutasteride-treated groups than in the control group, except for HIF-1 alpha protein. HIF-1 alpha and VEGF expression was similar in the 2.5 mg and 5.0 mg groups. Human prostate tissues demonstrated homogeneous staining of HIF-1 alpha 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-1 alpha and VEGF in rat prostates is suppressed by dutasteride. However, less than 4 weeks of dutasteride administration does not suppress the expression of HIF-1 alpha, 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.
ISSN
0036-5599
Language
English
URI
https://hdl.handle.net/10371/76742
DOI
https://doi.org/10.3109/00365590903337896
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