Expression and Significance of Microsomal Prostaglandin Synthase-1 (mPGES-1) and Beclin-1 in the Development of Prostate Cancer

Lu-Wei Xu,Ming Qian,Wen-Cheng Li,Rui-Peng Jia,Zheng Xu,Jian-Ping Wu,Xing-Guo Chen,Wen-Bin Huang

doi:10.7314/apjcp.2012.13.4.1639

Abstract

The aim of this study was to investigate the expression and significance of microsomal prostaglandin synthase-1 (mPGES-1) and Beclin-1 in the development of prostate cancer (PCa). Immunohistochemistry was performed on paraffin-embedded sections with rabbit polyclonal against mPGES-1 and Beclin-1 in 40 PCa, 40 benign prostatic hyperplasia (BPH) and 10 normal prostate specimens for this purpose. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for mRNA expression of mPGES-1 and Beclin-1, while MTT assays were used to ascertain the best working concentration of the mPGES-1 inhibitor (CAY10526). The effect of CAY10526 treatment on expression of Beclin-1 in DU-145 cells was studied using Western blot analysis. Localization of Beclin-1 and mPGES-1 was in endochylema. Significant differences in expression was noted among PCa, BPH and normal issues (P<0.05). Beclin-1 expression inversely correlated with mPGES-1 expression in PCa tissue (P<0.05). CAY10526 could significantly block mPGES-1 expression and the proliferation of DU-145 cells (P<0.05), while increasing Beclin-1 levels (P<0.05). Overexpression of mPGES-1 could decrease the autophagic PCa cell death. Inhibiting the expression of mPGES-1 may lead to DU-145 cell death and up-regulation of Beclin-1. The results suggest that inhibition of mPGES-1 may have therapeutic potential for PCa in the future.

Highlights

For the past few years, the incidence of prostate cancer (PCa) has a rising trend and it remains the most common cause of death among urologic malignance
Nakanishi has demonstrated that genetic deletion of microsomal prostaglandin synthase-1 (mPGES-1) could suppress intestinal and lung tumorigenesis in vivo animal trials (Nakanishi et al, 2008; Pecchi et al, 2008)
Hanaka et al (2009) has focused on the role of mPGES-1 in PCa. He found that mPGES-1 over-expressed in both PCa tissues and human PCa cell lines

Summary

Introduction

For the past few years, the incidence of PCa has a rising trend and it remains the most common cause of death among urologic malignance. Majority of PCa patients manifested androgen dependent prostate cancer (ADPC) in prophase of pathogenesis. Most patients will develop AIPC after the initiation of androgen deprivation. This development could account for most of the morbidity and mortality associated with this disease. Prostaglandin E2 (PGE2) which converted from arachidonic acid has been shown to play important roles in development and progression of PCa (Jain et al, 2008; Jia et al, 2008; Myung and Kim, 2008). Inhibition of PGE2 production could be achieved by blocking the cyclooxygenases (COX) with COX inhibitors such as celecoxib and etoricoxib, respectively. It is especially important to find other new drugs that target arachidonic acid metabolism and inhibit carcinogenesis

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