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

被引:11
作者
Xu, Lu-Wei [1 ]
Qian, Ming [1 ]
Jia, Rui-Peng [1 ]
Xu, Zheng [1 ]
Wu, Jian-Ping [1 ]
Li, Wen-Cheng [1 ]
Huang, Wen-Bin [2 ]
Chen, Xing-Guo [3 ]
机构
[1] Nanjing Med Univ, Nanjing Hosp Affiliated 1, Dept Urol, Nanjing, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Nanjing Hosp Affiliated 1, Dept Pathol, Nanjing, Jiangsu, Peoples R China
[3] Nanjing Med Univ, Nanjing Hosp Affiliated 1, Ctr Lab, Nanjing, Jiangsu, Peoples R China
关键词
Microsomal prostaglandin-E synthase-1; Beclin-1; prostatic neoplasms; AUTOPHAGY GENE; CELLS; APOPTOSIS; CYCLOOXYGENASE-2; TARGET; ADENOCARCINOMA; TUMORIGENESIS; BIOSYNTHESIS; PROSTACYCLIN; ACTIVATION;
D O I
10.7314/APJCP.2012.13.4.1639
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1639 / 1644
页数:6
相关论文
共 38 条
[1]   GPx2 counteracts PGE2 production by dampening COX-2 and mPGES-1 expression in human colon cancer cells [J].
Banning, Antje ;
Florian, Simone ;
Deubel, Stefanie ;
Thalmann, Sophie ;
Mueller-Schmehl, Katrin ;
Jacobasch, Gisela ;
Brigelius-Flohe, Regina .
ANTIOXIDANTS & REDOX SIGNALING, 2008, 10 (09) :1491-1500
[2]   Microsomal prostaglandin E synthase-1 inhibition blocks proliferation and enhances apoptosis in oesophageal adenocarcinoma cells without affecting endothelial prostacyclin production [J].
Beales, Ian L. P. ;
Ogunwobi, Olorunseun O. .
INTERNATIONAL JOURNAL OF CANCER, 2010, 126 (09) :2247-2255
[3]   Mechanism of Autophagy to Apoptosis Switch Triggered in Prostate Cancer Cells by Antitumor Cytokine Melanoma Differentiation-Associated Gene 7/Interleukin-24 [J].
Bhutia, Sujit K. ;
Dash, Rupesh ;
Das, Swadesh K. ;
Azab, Belal ;
Su, Zhao-zhong ;
Lee, Seok-Geun ;
Grant, Steven ;
Yacoub, Adly ;
Dent, Paul ;
Curiel, David T. ;
Sarkar, Devanand ;
Fisher, Paul B. .
CANCER RESEARCH, 2010, 70 (09) :3667-3676
[4]   Role and regulation of autophagy in cancer [J].
Chen, Ning ;
Karantza-Wadsworth, Vassiliki .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2009, 1793 (09) :1516-1523
[5]   Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function [J].
Cheng, Y ;
Wang, M ;
Yu, Y ;
Lawson, J ;
Funk, CD ;
FitzGerald, GA .
JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (05) :1391-1399
[6]   Autophagy inhibits reactive oxygen species-mediated apoptosis via activating p38-nuclear factor-kappa B survival pathways in oridonin-treated murine fibrosarcoma L929 cells [J].
Cheng, Yan ;
Qiu, Feng ;
Ye, Yuan-Chao ;
Guo, Zhao-Ming ;
Tashiro, Shin-Ichi ;
Onodera, Satoshi ;
Ikejima, Takashi .
FEBS JOURNAL, 2009, 276 (05) :1291-1306
[7]   Bcl-2 complexed with Beclin-1 maintains full anti-apoptotic function [J].
Ciechomska, I. A. ;
Goemans, G. C. ;
Skepper, J. N. ;
Tolkovsky, A. M. .
ONCOGENE, 2009, 28 (21) :2128-2141
[8]  
GAO X, 1995, CANCER RES, V55, P1002
[9]   Microsomal prostaglandin E synthase 1 determines tumor growth in vivo of prostate and lung cancer cells [J].
Hanaka, Hiromi ;
Pawelzik, Sven-Christian ;
Johnsen, John Inge ;
Rakonjac, Marija ;
Terawaki, Kan ;
Rasmuson, Agnes ;
Sveinbjornsson, Baldur ;
Schumacher, Martin C. ;
Hamberg, Mats ;
Samuelsson, Bengt ;
Jakobsson, Per-Johan ;
Kogner, Per ;
Radmark, Olof .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (44) :18757-18762
[10]   The current state of hormonal therapy for prostate cancer [J].
Hellerstedt, BA ;
Pienta, KJ .
CA-A CANCER JOURNAL FOR CLINICIANS, 2002, 52 (03) :154-179