886 ADENOVIRAL VECTOR EXPRESSING SHORT HAIRPIN RNA TARGETING G-PROTEIN COUPLED RECEPTOR (GPR87) HAS A STRONG ANTITUMOR ACTIVITY AGAINST GPR87-OVEREXPRESSING BLADDER CARCINOMAS

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research II1 Apr 2012886 ADENOVIRAL VECTOR EXPRESSING SHORT HAIRPIN RNA TARGETING G-PROTEIN COUPLED RECEPTOR (GPR87) HAS A STRONG ANTITUMOR ACTIVITY AGAINST GPR87-OVEREXPRESSING BLADDER CARCINOMAS Xia Zhang, dage liu, Shinsuke shibuya, Mikio Sugimoto, and Yoshiyuki kakehi Xia ZhangXia Zhang kagawa, Japan More articles by this author , dage liudage liu kagawa, Japan More articles by this author , Shinsuke shibuyaShinsuke shibuya kagawa, Japan More articles by this author , Mikio SugimotoMikio Sugimoto kagawa, Japan More articles by this author , and Yoshiyuki kakehiYoshiyuki kakehi kagawa, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.981AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES GPR87 belongs to G-protein coupled receptor family and had long been an orphan receptor. Recently, it was demonstrated that lysophosphatidic acid (LPA) was its ligand. LPA is a lipid mediator that is associated with several function including cellular proliferation and angiogenesis. Overexpression of GPR87 was found in many cancers including bladder cancer. Recent our studies revealed that the GPR87-overexpression affect the tumor progression through the induction of tumor-associated GPR87-targets in bladder cancer cell lines. Therefore, we performed experimental studies using a GPR87-suppressing adenoviral vector in order to establish the gene therapy against GPR87-overexpressing tumors. METHODS Three human bladder tumor cells with an overexpression of GPR87, including HT1197, RT112, and Tcssup cell lines, were used. We constructed adenoviral vector expressing shRNA targeting GPR87 (Ad-shGPR87). RESULTS The infection of Ad-shGPR87 effectively downregulated the GPR87 expression in all three GPR87-overexpressing tumor cell lines. Regarding the in vitro experiment, MTT assays demonstrated that the infection of Ad-shGPR87 significantly inhibited the growth of all three GPR87-overexpressing tumor cells (p<0.001, respectively). A flow cytometric analysis revealed the infection with Ad-shGPR87 into RT112 tumor cells to increase the percentage of apoptotic cells. Regarding in vivo experiments, a human tumor xenograft model in Scid mice was prepared by the implantation of GPR87-overexpressing tumors derived from RT112 cells. The antitumor effects were compared between the Ad-shGPR87 treatment group and the saline control group. Ad-shGPR87 or saline was administered by intratumoral injection every 4 days. Consequently, the Ad-shGPR87 treatment was found to have the strongest antitumor effect against the GPR87-overexpressing tumor xenografts (Fig.1A and 1B p<0.001). CONCLUSIONS Conclusions: The cancer gene therapy using the adenoviral vector expressing shRNA against GPR87 has a strong antitumor effect against GPR87-overexpressing tumors. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e360-e361 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Xia Zhang kagawa, Japan More articles by this author dage liu kagawa, Japan More articles by this author Shinsuke shibuya kagawa, Japan More articles by this author Mikio Sugimoto kagawa, Japan More articles by this author Yoshiyuki kakehi kagawa, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...