Investigation Of Relevance Between Cyclooxygenase-2 With Prostate Cancer

Prostate cancer (Pca) is the most commonly diagnosed form of canceramong men in the occident men, and is second only to lung cancer as a cause ofcancer-related death. Since last thirty years, disease incidence of prostatescarcinoma had increased quickly with elevation of living standard in ourcountry.Cyclooxygenase (COX), a prostaglandin H synthase, is a key enzyme thatcatalyzes the conversion of prostaglandins and other eicosanoids fromarachidonic acid. COX is involved in numerous processes, includinginflammation, inflammation, immune responses, blood coagulation,carcinogenesis and tumor progression. Two isoforms of COX have beenidentified: COX-1 and COX-2. COX-1 is considered to be the constituentisoforms involved in homeostasis of normal cell functioning. COX-2 is involvedin numerous processes, including carcinogenesis and tumor progression. It hasbeen reported that COX-2 was highly up regulated in a variety of epithelialmalignant neoplasms such as lung cancer, gastric carcinoma, colon carcinoma,cancer of the cervix and ovarian cancer. Cyclooxygenase-2 has been reported tobe correlated with tumor stages, tumor grade, malignancy degree and prognosis. Thus, COX-2 could become a potential molecular therapeutic target for cancertherapy.ObjectiveThe present study was designed to investigate the clinicopathologic andprognostic significance of COX-2 in Chinese patients with prostate cancer, andthe express of COX-2 in prostate cancer cell lines. Further, we detect effect ofCOX-2 selective inhibitors on prostate cancer cell lines. In order to find a newmarker for early diagnosis, judgemen of prognostic and a new potential targetfor cancer therapy.MethodFirstly, immunohistochemistry and RT-PCR was performed to detect theexpression of COX-2 in 88 prostate cancer tissue samples. The correlationbetween COX-2 expression and clinicopathologic factors and patient survivalwas evaluated. Next, Western blot assays and RT-PCR were performed to detectthe expression of protein and COX-2 mRNA in prostate cancer cell lines.Finally, We investigate effect of COX-2 selective inhibiter (Celecoxib) onprostate cancer cell lines by MTT, FCM and immunohistochemistry。ResultsThe levels of protein and COX-2 mRNA were significantly higher inprostate cancer tissues than in corresponding non-tumor and hyperplasia ofprostate gland tissues. COX-2 staining was positive in the cytoplasm of prostatecancer cells. High COX-2 expression was correlated with Gleason score, tumorstage, and lymph node status. Furthermore, patients with high COX-2expression showed lower disease-free and overall survival rates than those withlow COX-2 expression. Univariate and multivariate analyses suggested that thestatus of COX-2 expression was an independent prognostic indicator forpatients'survival.In our study, Western blot assays and RT-PCR were performed to detectthe expression of COX-2 protein and mRNA in prostate cancer cells. We selected a high-metastatic prostate cancer cell line (PC-3M) and threelow-metastatic prostate cancer cell lines (PC3, DU-145 and LNCaP). Weobserved that COX-2 was sufficiently expressed in all four prostate cancer celllines at both transcriptional and translational levels, and the levels of protein andCOX-2 mRNA expression showed significant difference among four humanprostate cancer cell lines. COX-2 in PC-3M which with high invasion expressedin high level.MTT assays, FCM detection and immunohistochemistry were performed toanalyze the effect of Celecoxib on cell life cycle and VEGF expression. Weobserved that COX-2 selective inhibiter could inhibit cell multiplication andcaryocinesia. Effected with Celecoxib , the expression of VEGF was downregulation.ConclusionTaken together, higher COX-2 expression might provide an independentprognostic marker for Chinese patients with prostate cancer who haveundergone surgery. COX-2 could become a new marker for early diagnosis,judgment of prognostic and a potential molecular therapeutic target for cancertherapy. In conclusion, the present study indicates that COX-2 might be apromising molecular marker for the clinical prognosis of human prostate cancerand a specific target for diagnosis of prostate cancer.