Shi Wen-Xia, Zhou Hong, Li Na, Huang Hong-Liang, Zhou Bao-Cheng
Jiangsu University, School of Medical Science and Laboratory Medicine, Zhenjiang 212013, China.
Zhonghua Zhong Liu Za Zhi. 2009 Jul;31(7):485-9.
To investigate the mechanisms that coagulation factor VIIa promotes proliferation and migration of a colon cancer cell line (SW620 cells) in vitro.
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.
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.
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.
探讨凝血因子VIIa促进结肠癌细胞系（SW620细胞）体外增殖和迁移的机制。
采用ELISA、Western印迹法和定量聚合酶链反应（QT-PCR）检测经因子VIIa或蛋白酶激活受体2激动剂（PAR2-AP）处理的SW620细胞中白细胞介素8（IL-8）、组织因子（TF）、半胱天冬酶-7和磷酸化p38丝裂原活化蛋白激酶（p-p38 MAPK）的表达。
因子VIIa和PAR2-AP在mRNA和蛋白水平均诱导IL-8表达，上调TF mRNA表达和TF活性，但下调SW620细胞中半胱天冬酶-7 mRNA和p-p38 MAPK水平。因子VIIa的作用不仅被抗TF抗体阻断，也被抗PAR2抗体阻断。
因子VIIa与细胞表面的TF结合，形成激活PAR2的复合物，进而刺激IL-8和TF表达，并抑制半胱天冬酶-7表达，从而促进肿瘤细胞增殖和迁移。p38 MAPK可能对这一过程起负向调节作用。
