INTRODUCTION - Inhibition of androgen synthesis by abiraterone acetate (AA) entails enhanced overall survival rates and clinical benefit for patients with locally advanced and metastasized prostate cancer (PC). The expression of heat shock protein 27 (HSP27) is generally associated with cytoprotection and was demonstrated to mediate chemoresistance under cytostatic therapy, for instance, docetaxel treatment.
In this study, we investigated the impact of AA treatment on HSP27 expression and PC cell growth.
METHODS - HSP27 expression levels in docetaxel and AA-treated PC cell lines LNCaP and PC-3 were determined by SDS PAGE and Western blot analysis. Proliferation assays were performed using a CASY Cell Counter and Analyzer Model TT (Roche Applied Science).
RESULTS - Despite significantly increased HSP27 expression in PC cells incubated with docetaxel, Western blot analysis implicated a significant reduction of the cytoprotective HSP27 in AA-treated PC cells. Notably, HSP27 stably overexpressed in PC-3-HSP27 cells did not appear as an HSP27-mediated proliferation benefit in the presence of AA as shown in docetaxel incubation studies.
CONCLUSIONS - In contrast to repeatedly demonstrated HSP27-driven chemoresistance related to chemotherapeutics, our results may constitute a broader molecular mode of action of AA chemotherapy. AA efficacy may exert an HSP27 suppressive role that goes beyond the primarily assumed inhibition of androgen biosynthesis.
Urologia internationalis. 2016 Mar 24 [Epub ahead of print]
Martin Weiss, Hannes Ahrend, Hannah Grossebrummel, Patrick Ziegler, Lars-Ove Brandenburg, Reinhard Walther, Uwe Zimmermann, Martin Burchardt, Matthias B Stope
Department of Urology, University Medicine Greifswald, Greifswald, Germany.