c-Jun/AP-1在因子Ⅶa促进SW620细胞增殖和迁移中的激活及其调控作用

Activation and regulation of c-Jun/AP-1 in factor Ⅶa-induced proliferation and migration of SW620 cells

目的探讨c-Jun/激活蛋白1(AP-1)在活化的凝血因子Ⅶa促进SW620细胞增殖、迁移过程中的作用及其调控机制。方法 Western blot检测人结肠癌SW620细胞中Ⅶa、组织因子(TF)、蛋白酶激活受体2(PAR2)、细胞外调节蛋白激酶1/2(ERK1/2)抑制剂U0126、p38抑制剂SB203580处理后c-Jun、磷酸化c-Jun(p-c-Jun)的蛋白水平变化;MTT和Transwell法分别检测AP-1抑制剂姜黄素对细胞增殖和细胞迁移能力的影响。结果单克隆抗TF和PAR2抗体、U0126均能抑制Ⅶa促进SW620细胞中c-Jun/AP-1活化的过程(P<0.05)。姜黄素降低Ⅶa诱导的SW620细胞增殖和细胞迁移能力(P<0.05)。结论 TF/Ⅶa复合物通过激活PAR2促进SW620细胞增殖和迁移,c-Jun/AP-1在此过程中被激活并发挥重要作用,ERK1/2为c-Jun/AP-1上游分子具有调控效应。

Objective To irvesfigate the effect and underlying mechanism of c-Jun/activator protein-l（AP-1） in factor Ⅶa-indUced proliferation and migration of SW260 cells. Methods The protein expressions of c-Jun and p-c-Jun treated with Ⅶa, tissue factor （TF）, protease-activated receptor 2（PAR2）, ERK1/2 inhibkor U0126 and p38 inhibitor SB203580 in colon cancer cell line SW620 were detected by Western blot. The proliferation and migration of SW620 cells were measured by MTT and Transwell assays, respectively. Results Factor Ⅶa promoted the protein expressions of c-Jun and p-c-Jun in a time-dependent manner, which was inhibited by anti-TF, anti-PAR2 antibodies and U0126 （P〈0. 05）. Cureumin attenuated Ⅶa-induced cell proliferation and migration in vitro （P〈0. 05）. Conclusion TF/Ⅶa complex enhances the proliferation and migration of SW620 cells via PAR2 activity, during which c-Jun/AP-1 is activated and regulated by the upstream molecule of ERK1/2.