Abstract
Introduction: Celecoxib is a selective cyclo-oxygenase-2 inhibitor that has been found in in vitro and in vivo models to inhibit carcinogenesis. We wanted to investigate the biological effects of celecoxib in patients with early prostate cancer. Methods: 45 patients with early prostate cancer were randomized to either celecoxib 400mg b.d. or no treatment for four weeks prior to their radical prostatectomy. Peri-operative prostatic tissue was obtained from the patients with biopsies sent for DNA microarray analysis of gene expression profiling. Histological sections were also stained and scored for biomarkers of cell proliferation, microvessel density, COX-2, apoptosis, angiogenic factors, and hypoxia, using immunohistochemical and immunofluorescent techniques. Comparisons were made between the celecoxib and control groups. As a parallel study, samples from different tissue origins were analyzed using DNA microarray, and comparisons of gene expression profiles were made based on tissue origin and histological status. Results: Celecoxib appeared to decrease tumour cell proliferation, microvessel density, angiogenesis, COX-2 expression, and hypoxia, as well as increase tumour apoptosis. These effects were borderline statistically significant in a multivariate model, but only the cell proliferation index approached statistical significance on univariate analysis. Further, multiple genes were differentially expressed in the celecoxib compared to the control group, most notably involving cell-to-cell communication, oxidative stress response, and tumour invasion and metastases. Interestingly, biopsies taken from cancerous prostate glands appeared to have similar gene expressions with each other, regardless of whether they actually contained cancer or not. This suggests a possible ‘field effect’ in the development of prostate cancer. Conclusions: Celecoxib appeared to have anti-cancer effects, via predominantly COX-2-independent mechanisms of action, which require further evaluation. The potential for a ‘field effect’ in tissue from patients with early prostate cancer is a novel and exciting finding that requires further investigation.