title: The TLR4/NF-κB signaling pathway mediates the growth of colon cancer.
abstract: OBJECTIVE
  We studied the involvement of the TLR4/NF-κB pathway in the growth of colon cancer using human colon cancer specimens, human colon cancer SW620 cell line, and nude mouse xenograft model.
  
  
  METHODS
  Tissue samples were surgically harvested. The human colon cancer SW620 cell line was pre-treated with the TLR4 inhibitor CRX-526 and stimulated with LPS. The nude mouse xenograft model was established by subcutaneous injection of SW620 cells with or without CRX-526, the TLR4 inhibitor. The study outcomes were mRNA and protein expressions of TLR4 and NF-κB p65 in specimens of colon cancer and adjacent normal tissue, SW620 cell line, and xenografts. In addition, we studied production of interleukin (IL)-6 and IL-8 in culture supernatants of LPS-stimulated SW620 cells.
  
  
  RESULTS
  Both mRNA and protein expressions of TLR4 and NF-κB in colon cancer specimens were higher than those in the adjacent normal tissue. LPS up-regulated expression of TLR4 and NF-κB, and stimulated production of IL-6 and IL-8 in SW620 cells. These effects were attenuated by CRX-526. TLR4 inhibition was also effective in the nude mouse xenograft model, as tumor sizes were significantly smaller, and expressions of TLR4 and NF-κB significantly lower, in the mice treated with CRX-526.
  
  
  CONCLUSIONS
  The TLR4/NF-κB signaling pathway is activated in colon cancer, causing production of IL-6 and IL-8, and, thereby, tumor growth and metastasization. Inhibition of TLR4 attenuates up-regulation of NF-κB and inhibits tumor growth.
authors.affiliation: Suizhou Central Hospital, Suizhou Hospital Affiliated to Hubei Pharmaceutical College, Zengdu District, Suizhou, Hubei Province, China. qianjin7601@163.com.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Huang
authors.forename: Z-J
authors.initials: ZJ
authors.lastname: Zhang
authors.forename: C-B
authors.initials: CB
authors.lastname: Cao
authors.forename: N
authors.initials: N
authors.lastname: Wang
authors.forename: F-F
authors.initials: FF
authors.lastname: Liu
authors.forename: J-Q
authors.initials: JQ
authors.lastname: Peng
authors.forename: X-J
authors.initials: XJ
authors.lastname: Ren
authors.forename: J
authors.initials: J
authors.lastname: Qian
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000502:physiology*; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: C501717:CRX-526; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D005944:Glucosamine