title: [Role of NF-κB in factor VIIa-induced proliferation and migration of colon cancer cell line SW620 cells].
abstract: OBJECTIVE
  To explore the roles of NF-κB in factor VIIa-induced proliferation and migration of a colon cancer cell line (SW620) in vitro and its possible mechanism.
  
  
  METHODS
  The expression levels of NF-κB (p65), inhibitory protein of NF-κB (IκB-α), caspase-7, interleukin 8 (IL-8) and tissue factor (TF) in SW620 cells treated with factor VIIa, PDTC (an inhibitor of NF-κB) and other factors were measured by Western-blotting and real-time PCR. Proliferation and migration of the cells were analyzed by flow cytometry and Transwell assay, respectively.
  
  
  RESULTS
  Factor VIIa down-regulated the IκB-α level in SW620 cells and increased the intranuclear level of NF-κB. Those effects of factor VIIa were blocked by anti-TF or anti-PAR2 antibodies. The effects of factor VIIa on proliferation and migration of SW620 cells, expression of IL-8, TF as well as caspase-7, were interfered by PDTC (the inhibitor of NF-κB).
  
  
  CONCLUSIONS
  TF/VIIa complex activates NF-κB pathway via PAR2, thereby up-regulates IL-8 and down-regulates caspase-7 expression in SW620 cells, finally promotes proliferation and migration of colon cancer cells. In addition, TF/VIIa/PAR2/NF-κB pathway also upregulates TF expression, thus to create a positive feedback loop of TF/VIIa/PAR2/NF-κB/TF.
authors.affiliation: School of Basic Medical Sciences and Laboratory Medicine, Jiangsu University, Zhenjiang, China.
authors.forename: Dong-lin
authors.initials: DL
authors.lastname: Guo
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.forename: Xian-mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Guo-ying
authors.initials: GY
authors.lastname: Xu
authors.forename: Hai-ping
authors.initials: HP
authors.lastname: Wen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D053179:Caspase 7 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D015942:Factor VIIa / Q000494:pharmacology*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C508606:CXCL8 protein, human; D020672:I-kappa B Proteins; D016209:Interleukin-8; C000606204:NFKBIA protein, human; C498143:RELA protein, human; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D013859:Thiocarbamates; D051996:Transcription Factor RelA; C066229:prolinedithiocarbamate; D000072000:NF-KappaB Inhibitor alpha; D013925:Thromboplastin; D011392:Proline; D015942:Factor VIIa; C505520:CASP7 protein, human; D053179:Caspase 7