MP01-08 GPX2 PROMOTES THE DEVELOPMENT OF BLADDER CANCER WITH SQUAMOUS DIFFERENTIATION THROUGH APOPTOSIS CONTROL

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I (MP01)1 Apr 2020MP01-08 GPX2 PROMOTES THE DEVELOPMENT OF BLADDER CANCER WITH SQUAMOUS DIFFERENTIATION THROUGH APOPTOSIS CONTROL Taku Naiki*, Aya Naiki-Ito, Toshiki Etani, Keitaro Iida, Ryosuke Ando, Takashi Nagai, Noriyasu Kawai, Satoru Takahashi, and Takahiro Yasui Taku Naiki*Taku Naiki* More articles by this author , Aya Naiki-ItoAya Naiki-Ito More articles by this author , Toshiki EtaniToshiki Etani More articles by this author , Keitaro IidaKeitaro Iida More articles by this author , Ryosuke AndoRyosuke Ando More articles by this author , Takashi NagaiTakashi Nagai More articles by this author , Noriyasu KawaiNoriyasu Kawai More articles by this author , Satoru Takahashi Satoru Takahashi More articles by this author , and Takahiro YasuiTakahiro Yasui More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000815.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Reactive oxygen species (ROS) have been identified as important chemical mediators in cell growth and differentiation. The glutathione redox system is the main mechanism protecting against the damage caused by ROS. We investigated the role and therapeutic potential of the glutathione redox system in bladder cancer. METHODS: The expression levels of glutathione peroxidase 2 (GPX2) and Ki-67 proteins were analyzed in human TUR specimens obtained from urethral carcinoma (UC) patients using immunohistochemistry; correlations between the GPX2 expression and prognosis were also analyzed. Further, male F344 rats were given 0.05% BBN in drinking water and 0.1% phenyl isothiocyanate in their diet for 36 weeks. Bladder tissue samples were collected from each animal for analyses. Furthermore, the rat cell line BC31 and human cell lines, were transfected with GPX2 siRNA and negative control siRNA (NC). Subsequently, the cell proliferation rates and ROS levels were investigated by cell counting, DCFH assay, western blotting, and flow cytometry. siRNA- or NC- transfected BC31 cells were subcutaneously implanted into nude mice. RESULTS: GPX2 was strongly expressed in low-grade and low-MIB-1 index cancers. PFS rates were significantly better in patients with higher GPX2 than in those with lower GPX2. Furthermore, GPX2 expression was significantly lower in the normal epithelium of the control group animals with bladder cancer than in the treated group. GPX2 expression was significantly higher in UC than in the normal epithelium with the strongest expression observed in cells with squamous differentiation. BC31 and RT4 cells strongly expressed GPX2 compared to the other cell lines. Silencing the GPX2 caused significant growth inhibition of BC31 and RT4 cells; the DCFH assay revealed significant reductions in the ROS levels in the siRNA-treated cells. Caspase-dependent apoptosis was found to be the cause of the decreased proliferation rates in the siRNA group. Notably, tumor growth was significantly inhibited in the BC31-implanted nude mice using the siRNA strategy for Gpx2. CONCLUSIONS: Our findings demonstrated that GPX2 plays several important roles in carcinogenesis through apoptosis regulation against intracellular ROS and may be a novel marker or therapeutic target in bladder cancer. Source of Funding: Grant-in-Aid for Scientific Research C (17K11153) The Ministry of Education, Culture, Sports, Science and Technology © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e4-e4 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Taku Naiki* More articles by this author Aya Naiki-Ito More articles by this author Toshiki Etani More articles by this author Keitaro Iida More articles by this author Ryosuke Ando More articles by this author Takashi Nagai More articles by this author Noriyasu Kawai More articles by this author Satoru Takahashi More articles by this author Takahiro Yasui More articles by this author Expand All Advertisement PDF downloadLoading ...