This basic science paper sets out to evaluate the effects that celecoxib, a selective cyclo-oxygenase-2 (COX-2) inhibitor, have on prostate cancer cell lines and evaluated the mechanisms behind these effects. COX-2 induces the production of prostaglandins, which promote cell proliferation and inflammation, and has been found to have increased levels in a number of malignancies including prostate cancer. Prostaglandins exert their effect on a number of G-protein coupled receptors, including the EP2 receptor. Of particular relevance is Prostaglandin-E2, which has a crucial role in angiogenesis and oncogenesis in prostate cancer. PGE-2 is also involved in cancer invasion and metastasis. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to have anti-tumour activity and in particular have been found to suppress androgen receptor activity. By means of western blotting, real-time polymerase chain reaction (PCR) and cell proliferation assay this study evaluated the effects of celecoxib on prostate cancer and the mechanisms behind them. The authors demonstrated that celecoxib inhibited prostate cancer growth by inducing cellular apoptosis. Furthermore, celecoxib was shown to reduce expression of messenger ribonucleic acid (mRNA) for the androgen receptor (AR) and prostate specific antigen (PSA). Celecoxib was also shown to inhibit EP2 expression. By using EP2 agonists and antagonists the authors were also able to demonstrate the importance of cAMP response element-binding (CREB), a transcription factor involved in the regulation of AR expression. An EP2 antagonist was also shown to suppress cell proliferation. The authors thus indicated that AR suppression by celecoxib is mediated by EP2 and CREB. They concluded that the EP2 receptor may be a novel target for intervention in advanced prostate cancer. This paper nicely sets out basic science techniques in the approach to acquiring novel targets for the treatment of advanced prostate cancer and provides the reader with an insight into the translational science of prostate cancer.
The EP2 receptor – a novel target for prostate cancer?
Reviewed by Edmund Chedgy
EP2 signaling mediates suppressive effects of clecoxib on androgen receptor expression and cell proliferation in prostate cancer.
CONTRIBUTOR
Edmund CP Chedgy
Vancouver Prostate Centre and University of British Columbia, Canada.
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