You have accessJournal of UrologyProstate Cancer: Basic Research VII1 Apr 20101292 INTERLEUKIN-6 CONFERS PROSTATE CANCER CELLS RESISTANCE TO BICALUTAMIDE VIA TIF2 Wei Lou, Meng Sun, Christopher Evans, and Allen Gao Wei LouWei Lou More articles by this author , Meng SunMeng Sun More articles by this author , Christopher EvansChristopher Evans More articles by this author , and Allen GaoAllen Gao More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.876AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The standard treatment for advanced, androgen-responsive prostate cancer is androgen-deprivation therapy with or without a nonsteroidal antiandrogen, such as bicalutamide. Although maximal androgen blockade exhibits favorable responses in the majority of patients, prostate cancer eventually become refractory and progresses. For patients on maximal androgen blockade who experience initial castration-resistance, the anti-androgen is removed as a second line hormonal manipulation. Patients only receiving androgen-deprivation therapy will have an anti-androgen added. These second-line hormonal manipulations will exhibit an approximate 3-month response in only a third of patients. The mechanism underlying bicalutamide resistance in the course of prostate cancer progression is incompletely understood. However, interleukin-6 (IL-6) plays a critical role in the development and progression of castration-resistant prostate cancer and herein we explored an association between IL-6 and bicalutamide resistance. METHODS Series of lower and higher passages of LNCaP cell sublines were generated by a long-term exposure of LNCaP cells in IL-6 containing culture medium. The cells were treated with bicalutamide and the cell number was counted. TIF2 mRNA and protein expression was analyzed by Northern blot and Western blot. The effect of TIF2 expression on IL-6 mediated bicalutamide resistance was analyzed by knock down TIF2 expression using siRNA. RESULTS The higher passages of LNCaP cells treated with IL-6 developed resistance to bicalutamide treatment compared to parental LNCaP cells. The levels of TIF2 in IL-6 treated LNCaP cells were found significantly higher than the parental LNCaP cells. Down regulation of TIF2 expression via shRNA in IL-6 treated LNCaP cells sensitized these cells to bicalutamide treatment; while over expression of TIF2 in the parental LNCaP cells increased resistance to bicalutamide. These results demonstrate that overexpression of IL-6 increases prostate cancer cells resistance to bicalutamide via TIF2. Furthermore, overexpression of IL-6 attenuated bicalutamide-mediated blockage of androgen-induced AR nuclear translocation and recruitment. CONCLUSIONS Overexpression of IL-6 not only plays important role in prostate cancer progression, but also contributes to bicalutamide resistance via TIF2. Our studies suggest that bicalutamide-IL-6 targeted adjunctive therapy that may lead to a more effective intervention than bicalutamide alone. Sacramento, CA© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e500 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wei Lou More articles by this author Meng Sun More articles by this author Christopher Evans More articles by this author Allen Gao More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...