High expression of cyclooxygenase-2 in uterine fibroids and its correlation with cell proliferation

ObjectiveTo investigate the expression of cyclooxygenase-2 (COX-2) in uterine fibroids and healthy uterine smooth muscle as well as its role in the pathogenesis of uterine fibroids.MethodsWe collected uterine fibroid tissues and their paired adjacent healthy uterine smooth muscle tissues from 30 cases of uterine fibroids. We used immunohistochemistry and quantitative real-time PCR, as well as western blot to detect COX-2 expression. Using the COX-2 inhibitors NS-398 and celecoxib, we observed the response to the inhibitors in the healthy and fibroid smooth muscle cell pairs.ResultsCOX-2 was detected by immunohistochemistry in both uterine fibroids and uterine smooth muscle, with higher immunoreactivity in uterine fibroids; the positive index of the smooth muscle cells was 11.90 and the positive index of uterine fibroids cells was 46.50 (P < 0.05). The expression of COX-2 mRNA in uterine fibroids was higher (0.122 ± 0.062) than in normal smooth muscle tissue (0.025 ± 0.009; P < 0.05). Also, the western blot results showed that COX-2 expression was significantly higher in uterine fibroid cases, as compared to the expression in uterine smooth muscle. Immunofluorescence showed that the occurrence of COX-2 was obviously higher in smooth muscle cells of uterine fibroids than in the healthy smooth muscle cells. NS-398 or celecoxib significantly inhibited the proliferation of smooth muscle cells of uterine fibroids, but did not inhibit the proliferation of healthy smooth muscle cells. Accordingly, NS-398 or celecoxib significantly reduced the expression of the downstream metabolite of COX-2, PGE2, in the smooth muscle cells of uterine fibroids, but not in healthy smooth muscle cells.ConclusionCOX-2 expression in uterine fibroids was significantly higher than in healthy uterine smooth muscles. The inhibition of COX-2 activity significantly reduced the proliferation of smooth muscle cells of the uterine fibroids, suggesting that COX-2 plays an important role in the pathogenesis of uterine fibroids.