Enzalutamide Enhances Glycolysis In Castration-Resistant Prostate Cancer

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (PD44)1 Sep 2021PD44-12 ENZALUTAMIDE ENHANCES GLYCOLYSIS IN CASTRATION-RESISTANT PROSTATE CANCER Wang Liu, Jean Li, Antonio Artigues, Si Yao, and Benyi Li Wang LiuWang Liu More articles by this author , Jean LiJean Li More articles by this author , Antonio ArtiguesAntonio Artigues More articles by this author , Si YaoSi Yao More articles by this author , and Benyi LiBenyi Li More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002058.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Glycolysis is a metabolic pathway that converts glucose into pyruvate, accompanied by ATP and NAPDH production. Compared with benign prostate tissue, increased glycolysis always occurs in prostate cancer cells, especially in neuroendocrinal progression of castration-resistant prostate cancer, to provide energy and intermediates of nucleic acid synthesis. As the widespread use of potent AR antagonists in castration-resistant prostate cancer patients, neuroendocrine progression (t-NEPC or CRPC-NE) has emerged as a major clinical obstacle, accounting for more than 25-30% mortality of prostate cancers. Therefore, we investigated the effect of AR antagonist on glycolysis in prostate cancer and provide theoretical basis for clinical treatment of prostate cancer. METHODS: Glycolysis-related gene expression profiles in prostate cancer were analyzed using the published cBioportal dataset (PMID: 26855148). Glucose consumption was assessed in LNCaP, C4-2B, 22RV1, DU145 and PC-3 cells after Enzalutamide treatment. Glucose uptake assay and glycolytic enzymes at protein expression levels were examined with drug treatment in dose-dependent and time-dependent manner. GAPDH expression in human prostate cancer specimens was evaluated using immunohistochemistry. RESULTS: Data mining for glucose transporters (GLUT) revealed that GLUT1 is the highest among all 14 Glut genes, of which GLUT3/10/14 were significantly lower while GLUT6/8 were significantly higher in NEPC compared to CRPC (Fig. 1A). For the 4 hexokinases (HK), HK1 is the dominant one among them but GCK mRNA expression was drastically increased in NEPC compared to CRPC (Fig. 1B). Other significantly increased glycolytic enzymes are ALDOC, ENO2 and PFKP (Fig. 1B). Glucose consumption were significantly increased after treatment with MDV3100 (10 μM) for 24 h in LNCaP, 22RV1 and PC-3 cells only with 2% cFBS, a FBS with reduced hormone levels (Fig. 2). Consistently, glucose uptake was significantly increased after Enzalutamide treatment in LNCaP, C4-2B, DU145 and PC-3 cells (Fig. 3). These effects were similar to insulin in all tested cells (Fig. 4). CONCLUSIONS: Gene expression of selective glycolytic enzymes was altered in NEPC specimens compared to CRPCs, of which the dramatic change is GCK upregulation in NEPC. AR antagonist treatment increased glucose consumption and uptake in prostate cancer cells, indicating an increased glycolysis of prostate cancer and contributing a potential mechanism for NE progression of CRPC patients. Source of Funding: DoD PCRP190026, NCI/GMaP3 and P20 GM103418 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e741-e741 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wang Liu More articles by this author Jean Li More articles by this author Antonio Artigues More articles by this author Si Yao More articles by this author Benyi Li More articles by this author Expand All Advertisement Loading ...