[Investigation of the mechanisms of coagulation factor VIIa-induced colon cancer SW620 cell proliferation and migration].
OBJECTIVE
To investigate the mechanisms that coagulation factor VIIa promotes proliferation and migration of a colon cancer cell line (SW620 cells) in vitro.


METHODS
The expression of interleukin 8 (IL-8), tissue factor (TF), caspase-7 and p-p38 MAPK in SW620 cells treated with factor VIIa or protease activated receptor 2 agonist (PAR2-AP) was measured by ELISA, Western-blotting and QT-PCR.


RESULTS
Factor VIIa and PAR2-AP induced IL-8 expression at both mRNA and protein levels, upregulated TF mRNA expression and TF activity, but down-regulated caspase-7 mRNA and p-p38 MAPK levels in SW620 cells. The effects of factor VIIa were not only blocked by anti-TF but also by anti-PAR2 antibodies.


CONCLUSIONS
Factor VIIa binds to TF on cell surface, forming a complex which activates PAR2, then provoking IL-8 and TF expression, and suppresses caspase-7 expression, thus promotes the tumor cell proliferation and migration. p38 MAPK may negatively regulate this process.
Shi
Wen-Xia
WX
Jiangsu University, School of Medical Science and Laboratory Medicine, Zhenjiang 212013, China.
Zhou
Hong
H
Li
Na
N
Huang
Hong-Liang
HL
Zhou
Bao-Cheng
BC
D053179:Caspase 7 / Q000096:biosynthesis / Q000235:genetics; 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; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D009842:Oligopeptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000819:agonists; D013925:Thromboplastin / Q000096:biosynthesis / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016209:Interleukin-8; D009842:Oligopeptides; D012333:RNA, Messenger; D044464:Receptor, PAR-2; C515807:seryl-leucyl-isoleucyl-glycyl-lysyl-valinamide; D013925:Thromboplastin; D048051:p38 Mitogen-Activated Protein Kinases; D015942:Factor VIIa; D053179:Caspase 7