324 TARGETED CYTOTOXIC ANALOG OF SOMATOSTATIN AN-162 [AEZS-124] INHIBITS PROLIFERATION OF PC-3 AND DU-145 HUMAN ANDROGEN-INDEPENDENT PROSTATE CANCERS IN VITRO AND IN VIVO

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research (II)1 Apr 2013324 TARGETED CYTOTOXIC ANALOG OF SOMATOSTATIN AN-162 [AEZS-124] INHIBITS PROLIFERATION OF PC-3 AND DU-145 HUMAN ANDROGEN-INDEPENDENT PROSTATE CANCERS IN VITRO AND IN VIVO Ferenc Rick, Andrew Abi-Chaker, Luca Szalontay, Norman Block, Gabor Halmos, and Andrew Schally Ferenc RickFerenc Rick Miami, FL More articles by this author , Andrew Abi-ChakerAndrew Abi-Chaker Miami, FL More articles by this author , Luca SzalontayLuca Szalontay Miami, FL More articles by this author , Norman BlockNorman Block Miami, FL More articles by this author , Gabor HalmosGabor Halmos Debrecen, Hungary More articles by this author , and Andrew SchallyAndrew Schally Miami, FL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1709AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The management of castration-resistant prostate cancer (CRPC) presents a clinical challenge because of limitations in durability and efficacy of current therapeutic modalities. A clear need exists for novel therapeutic strategies for the treatment of CRPC. Somatostatin receptors are expressed in human CRPC. Here we tested targeted somatostatin analog, AN-162, consisting of doxorubicin (DOX) conjugated to a somatostatin analog which acts as a carrier in cell lines of human androgen-independent prostate cancer in vitro and in vivo. METHODS Somatostatin receptor binding was measured with radioligand assays. Expression of mRNA for the five subtypes of the somatostatin receptor in PC-3 and DU-145 human prostate cancer cell lines was evaluated by RT-PCR. The effect of AN-162 and DOX on the viability of PC-3 and DU-145 cells was assessed by MTS assay. Nude mice bearing PC-3 and DU-145 tumors were randomized to 5 groups (control, AN-162, DOX, somatostatin analog RC-160 as a control, and DOX + RC-160). Treatment consisted i.v. injections of AN-162, DOX, RC-160, DOX + RC-160, or vehicle once a week for 4 weeks. Tumor volume was measured every week; the study lasted 28 days. The doses of AN-162 were equivalent to 1.45 mg/kg DOX (2.5 μmol/kg). RESULTS Specific, high-affinity binding sites for somatostatin were demonstrated. The PC-3 and DU-145 cell lines were each positive for the five subtypes of the somatostatin receptor. AN-162 and DOX (0.10-10 μM) inhibited the proliferation of PC-3 and DU-145 prostate cancer cells in a dose-dependent manner. In vivo, AN-162 exerted a stronger suppression of growth than DOX alone; but in vitro the difference was not statistically significant. In vivo, AN-162 significantly inhibited growth of both tumor models' compared with the controls and with the groups given equimolar doses of doxorubicin, RC-160, or doxorubicin plus RC-160. CONCLUSIONS Our work demonstrates potent inhibitory effects of AN-162 on somatostatin receptor positive androgen-independent prostate cancers The effects were greater than any of the components of AN-162. The mechanisms of action of targeted cytotoxic somatostatin analog, AN-162, in CRPC should be explored. Our findings suggest a possible use of AN-162 in these patients. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e131 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ferenc Rick Miami, FL More articles by this author Andrew Abi-Chaker Miami, FL More articles by this author Luca Szalontay Miami, FL More articles by this author Norman Block Miami, FL More articles by this author Gabor Halmos Debrecen, Hungary More articles by this author Andrew Schally Miami, FL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...