Expressions Of Membrane-associated PGE₂ Synthase And Cyclooxygenase-2 And The Effect Of Curcumincan

Background:Prostaglandin E₂,one of category arachidonic acid family,gradully increased with age growing.Recent study showed that COX-2 highly expressed in several tumors including prostatic carcinoma.Membrane-associated PGE₂ synthase (mPGE_s-1) is the last enzyme to produce PGE₂.mPGE_s-1 is another inducible enzyme following COX-2 in multiple physiological and pathophysiological progress,such as inflammation and tumor.The expression and fuction of mPGEs-1 in prostatic carcinoma have not been reported up to now.Curcumine extracted from curcuma has been considering as a latent third antineoplastic drug,and the anti-tumor mechanisms is versatile.One is implemented through repressing the activity of COX-2,and if curcumine inhibited cell multiplication of prostatic carcinoma through repressing the activity of mPGES-1 have not clear now.Objective:To detect two important inducible enzymes,mPGE_s-1 and COX-2,in tissues of prostatic carcinomas,and further analyze the relashionship between mPGE_s-1 and COX-2 expression in prostatic carcinoma.To detect the effect of curcumine on mPGE_s-1 and COX-2.To approach the metabolic pathway of prostagland in the development of prostate cancer.To investigate the new target for prostatic carcinoma drugs.Methods:The protein expression of mPGE_s-1 and COX-2 were detected by immunohistochemical assay in 30 tissues of PCa and 20 samples of BPH.The mRNA expression of mPGE_s-1 and COX-2 were detected by Real Time PCR.The protein expression of mPGE_s-1 and COX-2 were validate by immunohistochemical in PC3 cells.The results were analyzed by SPSS statistic software to discern by T test,Q test and linear correlation from ranks.Results:Negative(14/20) to weak expression(6/20) of mPGE_s-1 and COX-2 was found in BPH.In contrast,all of prostate cancer(30/30) tissues showed positive mPGE_s-1 and COX-2 protein expression.The over expression of mPGES-1 and COX-2 was correlated with the increasing of Gleason grade in PCa(P＜0.01).The level of mPGE_s-1 positively correlated with the level of COX-2(P＜0.01).The level of mRNA of COX-2 with curcumin was lower than that of mRNA expression without curcumin in PC3(P＜0.01).There was no effect of curcumin on mPGE_s-1(P＞0.05). The expression of COX-2 with curcumin was obvious lower than that If without curcumin(in PC3P＜0.01).The effect of curcumin on mPGE_s-1 had no difference than that without curcumin in PC3(P＞0.05).Conclusions:The proteins of mPGE_s-1 and COX-2 are over expressed and the level of mPGE_s-1 and COX-2 expression is positive correlated with Gleason grade in PCa.The level of mPGE_s-1 positively correlated with the level of COX-2.mPGEs-1 and COX-2 may have coupled actions in pathogenesis of prostate cancer.Curcumin can decrease of the protein and Mrna expression of COX-2,but have not suppression it in mPGE_s-1.