1570 TADALAFIL, THE PHOSPHODIESTERASE-5 INHIBITOR, ATTENUATES THE CELL GROWTH OF HUMAN BENIGN PROSTATIC HYPERPLASIA XENOGRAFTS IN SUPER-SCID MICE

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You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research1 Apr 20121570 TADALAFIL, THE PHOSPHODIESTERASE-5 INHIBITOR, ATTENUATES THE CELL GROWTH OF HUMAN BENIGN PROSTATIC HYPERPLASIA XENOGRAFTS IN SUPER-SCID MICE Hiroshi Kiuchi, Akira Tsujimura, Hidenobu Okuda, Keisuke Yamamoto, Shinichirou Fukuhara, Iwao Yoshioka, Tetsuya Takao, Yasushi Miyagawa, Norio Nonomura, and Taisei Nomura Hiroshi KiuchiHiroshi Kiuchi Suita, Japan More articles by this author , Akira TsujimuraAkira Tsujimura Suita, Japan More articles by this author , Hidenobu OkudaHidenobu Okuda Suita, Japan More articles by this author , Keisuke YamamotoKeisuke Yamamoto Suita, Japan More articles by this author , Shinichirou FukuharaShinichirou Fukuhara Suita, Japan More articles by this author , Iwao YoshiokaIwao Yoshioka Suita, Japan More articles by this author , Tetsuya TakaoTetsuya Takao Suita, Japan More articles by this author , Yasushi MiyagawaYasushi Miyagawa Suita, Japan More articles by this author , Norio NonomuraNorio Nonomura Suita, Japan More articles by this author , and Taisei NomuraTaisei Nomura Ibaraki, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1342AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Benign prostatic hyperplasia (BPH) is characterized by a pathologic proliferation of the prostate glandular and stromal tissues, and subsequent induction of lower urinary tract symptoms. Emerging evidences suggest that phosphodiesterase-5 (PDE-5) inhibitors improve urinary symptoms in patients with BPH. However, inhibition of prostate growth by PDE-5 inhibitors has not been fully elucidated. The objective of this study is to evaluate the effect of Tadalafil, the PDE-5 inhibitor, on suppression of prostate cell growth using a novel human BPH xenograft model. METHODS Human BPH tissue was obtained from a single patient who had undertaken retropubic prostatectomy for the treatment of BPH and was transplanted under the skin of super-SCID mice; SCID mice with macrophage dysfunction. BPH tissues were collected after 2 months of treatment with Tadalafil orally or nothing (control) with sustained release testosterone pellet. Immunohistochemical study was performed to examine the histology and expression of cell type-specific markers in xenografts, including PSA, androgen receptor (AR), p63 (basal cell marker), cytokeratin 8(K8, luminal cell marker) and human-specific CD31 (human vessel marker). We next assess the effect of Tadalafil on the prostate cell proliferation by Ki67 and apoptosis by cleaved caspase-3. Endothelial NOS (eNOS) and COX-2 expression were also examined. RESULTS The implanted tissue contained normal prostatic components; the gland showed two layers of epithelial cells. Inner layer expressed K8, AR and PSA, and outer layer was positive for p63. A considerable amount of the human originated vessels was apparent. After 2 months of Tadalafil treatment, a proliferation index (percentage of Ki-positive cells) was significantly reduced, compared with control in epithelial cells (1.4% vs. 3.9%, p<0.05) as well as in stromal tissues (51.7 vs.14.1 cells/mm2, p<0.05). Cleaved caspase-3 positive cells were significantly increased by Tadalafil. In addition, Tadalafil induced up-regulation of eNOS expression and down-regulation of COX-2 expression. CONCLUSIONS Our novel xenograft model has maintained appropriate histology and protein expression, and may serve as a useful human BPH model. Our study also indicates that Tadalafil attenuates the cell growth and induces apoptosis in benign prostate cells through NO signaling. These results provide a therapeutic potential of Tadalafil for reducing prostate volume in patients with BPH. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e636 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hiroshi Kiuchi Suita, Japan More articles by this author Akira Tsujimura Suita, Japan More articles by this author Hidenobu Okuda Suita, Japan More articles by this author Keisuke Yamamoto Suita, Japan More articles by this author Shinichirou Fukuhara Suita, Japan More articles by this author Iwao Yoshioka Suita, Japan More articles by this author Tetsuya Takao Suita, Japan More articles by this author Yasushi Miyagawa Suita, Japan More articles by this author Norio Nonomura Suita, Japan More articles by this author Taisei Nomura Ibaraki, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...