Pd35-09 Improved Prostate-Specific Membrane Antigen Stimulation Using a Super Additive Effect of Dutasteride and Lovastatin in Vitro

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III (PD35)1 May 2024PD35-09 IMPROVED PROSTATE-SPECIFIC MEMBRANE ANTIGEN STIMULATION USING A SUPER ADDITIVE EFFECT OF DUTASTERIDE AND LOVASTATIN IN VITRO Aleksandar Kuzmanov, Daniel Eberli, and Benedikt Kranzbühler Aleksandar KuzmanovAleksandar Kuzmanov , Daniel EberliDaniel Eberli , and Benedikt KranzbühlerBenedikt Kranzbühler View All Author Informationhttps://doi.org/10.1097/01.JU.0001009396.21455.74.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Improvement of PSMA-based detection of prostate cancer is facilitated by the high expression of prostate-specific membrane antigen (PSMA) in prostate cancer. However, limitation for this promising diagnostic tool comes from the observed low PSMA surface expression in certain patients. PSMA induction by pharmacological agents might be able to improve the detection rate of PSMA-based imaging. Therefore, in the present study we compared the singular effects of dutasteride (Duta) and lovastatin (Lova) on cell viability and PSMA expression. In addition, we tested if a combination treatment using lower concentrations of Duta and Lova can further induce PSMA expression. METHODS: LNCaP, C4-2 and VCaP cells were treated for 7 to 14 days with different concentrations of Duta (0.25, 0.5 and 1 μM), Lova (0.5, 1, 2, 5, 10 μM) or a combination of Duta+ Lova (0.125 μM Duta+0.5 μM Lova, 0.25 μM+0.5 μM, 0.5 μM+0.5 μM, 0.125 μM+1 μM, 0.25 μM+1 μM, 0.5 μM+1 μM). PSMA surface expression was assessed using immunocytochemistry. Total PSMA and AR expression was analyzed by capillary western immunoassay (WES). RESULTS: Treatment of LNCaP cells with 0.25 μM (166±25%, p<0.05), 0.5 μM (217±44%, p<0.01) and 1 μM Duta (333±75%, p<0.001) led to a significant increase in total PSMA expression compared to vehicle control. Furthermore, total PSMA expression was significantly increased following treatment of LNCaP cells with 1 μM (167±35%, p<0.01), 2 μM (225±52%, p<0.001), 5 μM (242±66%, p<0.001) and 10 μM (267±74%, p<0.001) of Lova compared to control. A combination treatment of LNCaP cells using 0.5 μM Duta+0.5 μM Lova (288±42%), 0.25 μM Duta+1 μM Lova (280±44%) and 0.5 μM Duta+1 μM Lova (340±65%) led to a further significant increase in total PSMA expression compared to single compound treatment using 1 μM Duta (168±24%) or 1 μM Lova (160±22%).Lova treatment significantly decreased AR protein levels in LNCaP cells (1 μM: 88% ± 3%, 2 μM: 76% ± 4%, 5 μM: 52% ± 3%, 10 μM: 26% ± 2%). In LNCaP cells, total AR expression upon combination treatment of Duta+ Lova did not show any additional decrease compared to single compound treatment using 1 μM Duta or 1 μM Lova. In C4-2 cells, AR expression was further reduced using 0.5 μM Duta+1 μM Lova (52±2%) compared to treatment with 1 μM Lova (77±3%). CONCLUSIONS: Our data show a significant induction of PSMA expression upon treatment of different prostate cancer cell lines with lovastatin. Furthermore, combination treatment using lower concentrations of dutasteride and lovastatin further enhances PSMA expression compared to a single compound treatment. Source of Funding: Max und Hedwig Niedermaier-Stiftung © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e728 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Aleksandar Kuzmanov More articles by this author Daniel Eberli More articles by this author Benedikt Kranzbühler More articles by this author Expand All Advertisement PDF downloadLoading ...