因子Ⅶa依赖组织因子激活PAR2/ERK/NF-κB抑制结肠癌SW620细胞caspase-3表达
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江苏省自然科学基金(BK2010336)。


Factor Ⅶa decreases the expression of caspase-3 in colon cancer SW620 cells via the activation of PAR2/ERK/NF-κB by tissue factor
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    摘要:目的:探讨凝血因子Ⅶa对结肠癌SW620细胞增殖能力以及表达凋亡分子天冬氨酸特异性半胱氨酸蛋白酶3(caspase-3)的影响及其作用机制。 方法:用一定剂量的蛋白酶激活受体2激动剂(PAR2-AP)、凝血因子Ⅶa等刺激物处理SW620细胞,观察细胞生长情况;western blot和定量PCR分别检测细胞表达caspase-3蛋白质及mRNA水平;利用相关抗体、拮抗剂和抑制剂等观察因子Ⅶa对caspase-3表达的效应变化。 结果:PAR2-AP(100 μmol/L)及因子Ⅶa(10 nmol/L)能够明显促进SW620细胞的生长,减少细胞caspase-3蛋白质和mRNA的表达;抗组织因子(TF)抗体(а-TF)、PAR2拮抗剂(PAR2-аAP)、ERK1/2抑制剂U0126以及NF-κB抑制剂PDTC均能逆转因子Ⅶa对SW620细胞caspase-3表达的抑制效应,而p38MAPK抑制剂SB203580对caspase-3的表达无明显的干预作用。 结论:因子Ⅶa依赖TF活化PAR2,经ERK1/2和NF-κB信号通路,抑制SW620细胞caspase-3表达,从而促进细胞的增殖与生长。

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    Abstract: Objective:To explore the effects of coagulation factor Ⅶa on the proliferation of colon cancer cells SW620 and the expression of apoptotic molecule caspase-3, as well as the mechanisms involved in the process. Methods:SW620 cells were treated with protease activated receptor-2 agonists (PAR2-AP) and coagulation factor Ⅶa respectively, then the proliferation rate of the cell was observed. Meanwhile, the expression levels of caspase-3 protein and mRNA in SW620 cells were detected by western blot and quantitative real-time PCR (QT-PCR), respectively. The specific antibody to tissue factor (а-TF), antagonist for PAR2 (PAR2-аAP) and inhibitors for ERK1/2 (U0126), NF-κB (PDTC) and p38MAPK (SB203580) were used to investigate the effects of factor Ⅶa on the expression of caspase-3. Results:After the treatment of PAR2-AP (100 μmol/L) and factor Ⅶa (10 nmol/L), the growth of SW620 cells was promoted significantly and the expression of caspase-3 protein and mRNA in the cells was downregulated. The inhibitory effect of factor Ⅶa on the expression of caspase-3 in SW620 cells was obviously reversed by a-TF, PAR2-aAP, U0126 and PDTC, but not by SB203580. Conclusion:Factor Ⅶa inhibited the expression of caspase-3 in SW620 cells, then promoted the proliferation and growth of SW620 cells via TFactivated PAR2 and ERK1/2/NF-κB signal pathway.

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张先梅,周红,陈东东,解鸿翔,胡丽超,武标,吴莺.因子Ⅶa依赖组织因子激活PAR2/ERK/NF-κB抑制结肠癌SW620细胞caspase-3表达[J].临床检验杂志,2012,30(4):284-288

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  • 收稿日期:2011-09-26
  • 最后修改日期:2011-11-22
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  • 在线发布日期: 2012-05-22
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