Effects of selective cyclooxygenase-2 inhibitor (celecoxib) in patients with advanced endometriosis : in-vivo and in-vitro effect

Abstract

Endometriosis, defined as the proliferation of endometrial tissue outside the uterine cavity, is one of the most common benign gynecologic disorders. Unfortunately, there is no effective treatment of endometriosis with fewer side effects. Cyclooxygenase (COX)-2 inhibitors show great promise in this respect. COX-2, involved in the inhibition of apoptosis and the potentiation of cell growth, is frequently overexpressed in human endometrial cells. The purpose of this study is to investigate the effects of celecoxib (Celebrex®), a selective cyclooxygenase-2 inhibitor, on human endometrial cells in vitro and to analyze the effect of celecoxib on growth of endometrial cells in vivo and the molecular mechanism of celecoxib-induced cell growth inhibition and cell apoptosis. A total of 98 patients diagnosed with advanced-stage endometriosis (stages III and IV) were included in this study. The patients were divided into two groups; group A (n=49) received a single course of oral celecoxib (Celebrex®, 200 mg/C, twice a day for two weeks) before surgery; group B (n=49) received no medication before surgery and endometriosis was confirmed by histological examination in all patients. In the present study, celecoxib induced the cell cycle arrest in the G2/M phase and cell apoptosis. The expression of the mRNA for COX-2 in eutopic endometrium and ovarian endometriotic tissue was investigated by RT-PCR. COX-2 expression were significantly higher in eutopic endometrium and ovarian endometriotic tissue of women with group B compared with group A regardless of the menstrual cycle. Expression of NF-κB-p65 and c-myc in eutopic endometrium and ovarian endometriotic tissue regardless of menstrual cycle were significantly higher in women with group B compared with group A. This study has demonstrated the effect of celecoxib on MMP-2 and MMP-9 mRNA both in eutopic endometrium and ovarian endometriotic tissue. The results showed a significant decrease in MMP-2 and MMP-9 mRNA levels in group A, compared with group B regardless of the menstrual cycle.This study hypothesize that celecoxib may have anti-proliferative effect through inhibition of cell cycle progression and induces apoptosis in human endometrial stromal cells in a dose-dependent manner. In the present study, celecoxib exerts anti-inflammatory effects and inhibited the angiogenesis, adhesion by suppression of NF- κB translocation and may be beneficial in the treatment of endometriosis-associated symptoms. This study suggest that celecoxib may have potential clinical benefit in endometriosis and might be efficacious for the treatment of endometriosis before surgery