326 GLUTATHIONE PEROXIDASE 2 IS A POTENTIAL THERAPEUTIC MOLECULE FOR CASTRATION-RESISTANT PROSTATE CANCER

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You have accessJournal of UrologyProstate Cancer: Basic Research (II)1 Apr 2013326 GLUTATHIONE PEROXIDASE 2 IS A POTENTIAL THERAPEUTIC MOLECULE FOR CASTRATION-RESISTANT PROSTATE CANCER Taku Naiki, Makoto Asamoto, Aya Naiki-Ito, Noriyasu Kawai, Ryosuke Ando, Toshiki Etani, Keiichi Tozawa, Kenjiro Kohri, and Satoru Takahashi Taku NaikiTaku Naiki Ngoya, Japan More articles by this author , Makoto AsamotoMakoto Asamoto Nagoya, Japan More articles by this author , Aya Naiki-ItoAya Naiki-Ito Nagoya, Japan More articles by this author , Noriyasu KawaiNoriyasu Kawai Nagoya, Japan More articles by this author , Ryosuke AndoRyosuke Ando Nagoya, Japan More articles by this author , Toshiki EtaniToshiki Etani Nagoya, Japan More articles by this author , Keiichi TozawaKeiichi Tozawa Nagoya, Japan More articles by this author , Kenjiro KohriKenjiro Kohri Nagoya, Japan More articles by this author , and Satoru TakahashiSatoru Takahashi Nagoya, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1711AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer generally acquires a castration-resistant growth capacity with progression, resulting in resistance to anti-androgen therapy. Therefore, identification of the genes regulated through this process may be important in understanding the mechanisms of prostate cancer. We previously established a new castration-resistant prostate cancer (CRPC) metastatic model, and analyzed its gene expression using microarray. Among the overexpressed genes in CRPC, glutathione peroxidase 2 (GPX2) was included. GPX is a key molecule of the glutathione redox system in humans: however, no reports has described the relation between CRPC and GPX2.Therefore, we investigated the role of GPX2 in CRPC. METHODS Immunohistochemical analyses of GPX2 was performed using tissue microarray of prostatectomy specimens with or without neoadjuvant hormonal therapy. Next, GPX2 siRNA and negative control (NC) siRNA were used to transfect PCai1 and PC3 cells. After transfection, we investigated the proliferation rate and ROS by cell counts, DCFH assay for ROS detection, western blotting, and flowcytometry. In addition, siRNA- or NC- transfected cells diluted in buffered solution were subcutaneously implanted into normal and castrated nude mice. Three weeks after implantation, mice were sacrificed. RESULTS Silencing of GPX2 with an iRNA strategy caused a significant growth inhibition of androgen-independent PCai1 and PC3 cells, and the DCFH assay results revealed that intracellular ROS levels were significantly elevated in siRNA-treated groups, and the decrease in proliferation rate in the siRNA group was due to cyclin B1-dependent cell cycle arrest. Furthermore, knock-down of the Gpx2 expression of PCai1 in vivo significantly inhibited tumor growth compared with negative controls in castrated mice (Figure). In the immunohistochemical analyses of human prostatectomy specimens, GPX2 expression was significantly higher in residual cancer foci after neoadjuvant hormone therapy than in hormone naïve prostate cancer foci. CONCLUSIONS These findings suggest that GPX2 might play an important role in the proliferation of prostate cancer in the castration condition against ROS signaling, and might be therapeutic target for CRPC. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e132 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Taku Naiki Ngoya, Japan More articles by this author Makoto Asamoto Nagoya, Japan More articles by this author Aya Naiki-Ito Nagoya, Japan More articles by this author Noriyasu Kawai Nagoya, Japan More articles by this author Ryosuke Ando Nagoya, Japan More articles by this author Toshiki Etani Nagoya, Japan More articles by this author Keiichi Tozawa Nagoya, Japan More articles by this author Kenjiro Kohri Nagoya, Japan More articles by this author Satoru Takahashi Nagoya, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...