Expression And Significance Of MPGES-1 In Prostate Cancer

Background: Prostate cancer (Pca) is a common male malignant neoplasm. The morbidity and mortality has a rising trend in the past few years. The occurrence of Pca was the tenth leading cause of male cancer and the first place of urogenital neoplasms in our country. Pca is seriously harming to men's health. Majority of PCa patients manifested androgen dependent prostate cancer(ADPC) in prophase of pathogenesis. However, most patients will develop AIPC after the initiation of androgen deprivation. The exact mechanism of transformation remained not clear and there is no any effective therapy for this disease today. Therefore, further studies will be needed to investigate the pathogenesis and therapy of Pca. Membrane bound prostaglandin E2 synthase-1(mPGES-1) is an important terminal inducible enzyme which mediates the synthetic of Prostaglandin E2(PGE2) and plays an important role in carcinogenesis and development of Pca. Downregulating the expression of mPGES-1 could decrease the vitality of AIPC cells and increase apoptosis and make a decrement of the rate of oncogenesis in nude mouse. Otherwise, another considering factor is that downregulating autophagy of Pca cells could make them survival. Inducing cancer cells autophagy could trigger the autophagic death and increase the sensibility to antitumor drug by upregulating the Beclin-1.However, in Pca, it is not clear that mPGES-1 could effect on Beclin-1 to affect the development of Pca whether or not.Objective: To research the expression characteristics of mPGES-1 and Beclin-1 in different prostate tissues and investigate the significance of mPGES-1 effecting on Beclin-1.Methods: Immunohistochemistry was performed on paraffin-embedded sections with rabbit polyclonal against mPGES-1 and Beclin-1 in 40 Prostate Cancer(PCa) and 40 benign prostatic hyperplasia (BPH) and 5 normal prostate specimens to explore the relationship of the expression of mPGES-1 and Beclin-1. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to study the expression of mPGES-1 and Beclin-1 on mRNA levels in above three specimens. Applying different concentration of mPGES-1 inhibitor(CAY10526) intervened DU-145 cells and erecting complete medium (CM) group and serum-free medium(SF) group. The purpose of MTT assay is to ascertain the best working concentration of CAY10526. The effect of CAY10526 treatments on the expression of Beclin-1 in DU-145 cells was studied using Western blot analysis.Results: A significant difference of mPGES-1 and Beclin-1 expression was found among PCa, BPH and normal issues,respectively(P<0.05).Beclin-1 expression was inversely correlated with mPGES-1 expression in PCa tissue(P<0.05). There was obviously negative correlation between mPGES-1 and Beclin-1 in PCa(r=-0.427 P<0.05). The positive rate of mPGES-1 in AIPC was significantly higher than that in ADPC (P<0.05). A significant association was observed between mPGES-1 expression and higher Gleason scores(p<0.05) and tumor stage(P<0.05).However, there was no significant association between mPGES-1 expression and age(P>0.05). A significant association was observed between Beclin-1 expression and lower Gleason scores (P < 0.05) and tumor stage (P < 0.05),the Beclin-1 expression has no significant association with age(P>0.05).CAY10526 could significantly block mPGES-1 expression and the proliferation of DU-145 cells(P<0.05). DU-145 cells cytoactive descended with the does of CAY10526 increasing from 10 to 50μM although there is a plateau phase beyond 20μM. The expression of Beclin-1 in the SF group was higher than that in the CM group(P<0.05). After being intervened by CAY10526 at 10μM, Beclin-1 expression down-regulated, however, the expression of Beclin-1 remained higher than that in control group (P<0.05). Nevertheless, with the cytoactive decreasing, mPGES-1 and Beclin-1 both down-regulated significantly (P<0.05).Conclusion: mPGES-1 may play an important role in progression and transformation of androgen independent.Inhibiting mPGES-1 could decrease cytoactive of Pca cells significantly and effectively. That mPGES-1 would be an significant therapeutic target should be a further research.