Sodium selenite inhibits the expression of VEGF, TGFbeta(1) and IL-6 induced by LPS in human PC3 cells via TLR4-NF-(K)B signaling blockage.
Lipopolysaccharide (LPS)-induced TLR4-NF-(K)B signaling plays an important role in the development of prostatic tumors from chronic bacterial prostatic infection. Although many studies support the role of selenium in protecting against the development of prostate cancer secondary to chronic prostatitis, the mechanism of action remains unclear. The aim of our study was to investigate whether selenium inhibits the LPS-induced TLR4 signaling pathway in human prostate cancer PC3 cells. Using real-time quantitative PCR and ELISA analysis, we found that pretreatment with selenium (0.5-5uM) inhibited the LPS-induced expression of TGFbeta(1) and VEGF and production of these cytokines and IL-6 by PC3 cells, but did not alter the expression of TLR4 mRNA. Further experiments using Western blot showed that selenium at 3 and 5uM significantly inhibited the translocation of the NF-(K)B p65 subunit to the nucleus in LPS-stimulated PC3 cells. Our results suggest that low doses of selenium may protect the prostate from prostatitis-induced cancer by inhibiting nuclear translocation of the NF-(K)B and the subsequent production of the immunosuppressive cytokine TGFbeta(1), proangiogenic factor VEGF and pro-inflammatory factor IL-6.
Pei
Zengyang
Z
College of Veterinary Medicine, China Agricultural University, Beijing, China.
Li
Hui
H
Guo
Ying
Y
Jin
Yipeng
Y
Lin
Degui
D
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007114:Immunization; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D018038:Sodium Selenite / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D018038:Sodium Selenite