LR4 signaling promotes secretion of VEGF/IL-8 in prostate cancer PC3 cells and related mechanism
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Supported by National Natural Science Foundation of China(30771984, 30972688).

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    Abstract:

    bjectiveTo study TLR4 expression in human prostate cancer PC3 cells and the related intracellular signaling mechanisms.MethodsHuman prostate cancer PC3 cells were stimulated with TLR4-specific ligand lipopolysaccharide(LPS), then the cells and supernatants were collected 0, 2, 6, 12, 24, and 48 hours after LPS stimulation.TLR4 mRNA and protein expression was examined by reverse transcription-PCR and Western blotting analysis, respectively.The mRNA expression of TGF-β, VEGF, IL-8, COX-2, and MMP3 was also measured by reverse transcription-PCR, and the levels of VEGF, IL-8 in the supernatants were examined by ELISA.To further study the related signaling pathway, MAPK and NF-κB signaling pathways were blocked by specific inhibitors in PC3 cells before LPS stimulation; the cells were collected after 4 hours and the supernatants were collected after 24 hours; and the above mentioned factors were examined by reverse transcription-PCR and ELISA again.ResultsTLR4 expression was up-regulated by LPS stimulation in human prostate cancer PC3 cells, which significantly increased mRNA expression of TGF-β, VEGF, IL-8, COX-2, and MMP3 and secretion of VEGF and IL-8 in the supernatants (P<0.05); further study showed that p38 MAPK and NF-κB signal pathways were involved in the process.ConclusionTLR4 signaling promotes VEGF and IL-8 secretion through p38 MAPK and NF-κB signal pathways.

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History
  • Received:March 14,2010
  • Revised:May 28,2010
  • Adopted:June 01,2010
  • Online: July 21,2010
  • Published:
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