Expression and significance of microsomal prostaglandin synthase-1 (mPGES-1) and Beclin-1 in the development of prostate cancer.
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.
Department of Urology, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing, China.
Lu-Wei
LW
Xu
Ming
M
Qian
Rui-Peng
RP
Jia
Zheng
Z
Xu
Jian-Ping
JP
Wu
Wen-Cheng
WC
Li
Wen-Bin
WB
Huang
Xing-Guo
XG
Chen
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000378:metabolism*; D000071186:Beclin-1; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016009:Chi-Square Distribution; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D000071876:Prostaglandin-E Synthases; D011467:Prostate / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D013876:Thiophenes / Q000494:pharmacology; D015854:Up-Regulation
C569291:4-(benzo(b)thiophen-2-yl)-3-bromo-5-hydroxydihydrofuran-2(3H)-one; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D013876:Thiophenes; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D015107:4-Butyrolactone