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  

Factor Ⅶa decreases the expression of caspase-3 in colon cancer SW620 cells via the activation of PAR2/ERK/NF-κB by tissue factor

作　　者：张先梅[1] 周红[1] 陈东东[1] 解鸿翔[1] 胡丽超[1] 武标[1] 吴莺[2] 

机构地区：[1]江苏大学基础医学与医学技术学院,江苏镇江212013 [2]江苏大学附属医院内科,江苏镇江212013

出　　处：《临床检验杂志》2012年第4期284-288,共5页Chinese Journal of Clinical Laboratory Science

基　　金：江苏省自然科学基金(BK2010336)

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(100μmol/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。Objective To explore the effects of coagulation factor Ⅶa on the proliferation of colon cancer cells SW620 and the expres- sion 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 VHa respectively, then the proliferation rate of the cell was ob- served. Meanwhile, the expression levels of caspase-3 protein and mRNA in SW620 cells were detected by western blot and quantita- tive real-time PCR （ QT-PCR）, respectively. The specific antibody to tissue factor （ a-TF）, antagonist for PAR2 （PAR2-aAP） and in- hibitors for ERK1/2 （U0126）, NF-KB （PDTC） and p38MAPK （SB203580） were used to investigate the effects of factor Wlla on the expression of caspase-3. Results After the treatment of PAR2-AP （ 100 μmol/L） and factor Wlla （ 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 V^a 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-KB signal pathway.

关 键 词：凝血因子Ⅶa 组织因子 蛋白酶激活受体2 天冬氨酸特异性半胱氨酸蛋白酶3 

分 类 号：Q813[生物学—生物工程] R735.35[医药卫生—肿瘤]