1435 THE USE OF SIMVASTATIN AND EZETIMIBE AS NOVEL THERAPEUTICS FOR PROSTATE CANCER IN A XENOGRAFT MODEL (2010)

You have accessJournal of UrologyProstate Cancer: Basic Research VIII1 Apr 20101435 THE USE OF SIMVASTATIN AND EZETIMIBE AS NOVEL THERAPEUTICS FOR PROSTATE CANCER IN A XENOGRAFT MODEL Elizabeth Masko, Lionel L. Banez, Nikolaos A. Valilis, Tameika E. Phillips, Susan H.M. Poulton, Keith R. Solomon, Salvatore V. Pizzo, and Stephen J. Freedland Elizabeth MaskoElizabeth Masko Durham, NC , Lionel L. BanezLionel L. Banez Durham, NC , Nikolaos A. ValilisNikolaos A. Valilis Durham, NC , Tameika E. PhillipsTameika E. Phillips Durham, NC , Susan H.M. PoultonSusan H.M. Poulton Durham, NC , Keith R. SolomonKeith R. Solomon Boston, MA , Salvatore V. PizzoSalvatore V. Pizzo Durham, NC , and Stephen J. FreedlandStephen J. Freedland Durham, NC View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1128AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Statins, the most widely used class of drugs, effectively lower serum cholesterol by inhibiting the enzyme HMG-coA reductase. Although primarily given to reduce the risk of cardiovascular disease, recent data suggest statins do not prevent the occurrence of prostate cancer (PCa), but may reduce PCa progression. This implies that statins may be more useful as therapy than as chemoprevention. However, the process by which statins slow tumor growth, whether by lowering cholesterol or via their non-cholesterol mechanisms remains unknown. We hypothesize that simvastatin will slow PCa growth, but simvastatin and the cholesterol uptake inhibitor ezetimibe will be better than either alone. METHODS A total of 100 nude mice were injected with the human PCa cell line LAPC-4, and placed on a high fat, high cholesterol Western diet (17% protein-43% carbohydrate-40% fat kcal, 1.25% cholesterol) ad libitum. Two weeks post-injection, all mice were randomized to 1 of 4 groups: control (no intervention), simvastatin (11mg/kg), ezetimibe (30mg/kg), or simvastatin + ezetimibe. Mice received continuous simvastatin via subcutaneous implantation of osmotic pumps, and ezetimibe through their diet. Tumors and body weights were measured twice weekly. All mice were sacrificed 42 days post-randomization (duration of pump dispensing). RESULTS At Day 42 of study, mice in the simvastatin + ezetimibe group had tumors that were 62-100% larger than either the control or ezetimibe groups (p<0.01). The combination group also trended to have larger tumors than the simvastatin group (p=0.18). There were no differences in tumor volumes between any other groups (all p>0.05). Body weights were similar among all groups throughout the study (p>0.06). Control mice had the largest liver weights (p=0.0001), although bilirubin, AST, and ALT analysis showed no differences in liver function among all groups (p>0.05). Cholesterol and triglyceride analyses are pending. CONCLUSIONS LAPC-4 xenograft mice fed a high fat, high cholesterol Western diet and treated with simvastatin or ezetimibe showed no significant difference in tumor volume compared to control. Contrary to our hypothesis, combination therapy of simvastatin + ezetimibe promoted tumor growth in our model. This is consistent with some clinical data suggesting this combination in humans may promote cancer development, but this point remains controversial, as conflicting human data exists. Further mechanistic studies are planned to explore the mechanisms underlying the growth promoting effects of the combination of simvastatin and ezetimibe. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e553 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Elizabeth Masko Durham, NC More articles by this author Lionel L. Banez Durham, NC More articles by this author Nikolaos A. Valilis Durham, NC More articles by this author Tameika E. Phillips Durham, NC More articles by this author Susan H.M. Poulton Durham, NC More articles by this author Keith R. Solomon Boston, MA More articles by this author Salvatore V. Pizzo Durham, NC More articles by this author Stephen J. Freedland Durham, NC More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...