凝血因子Ⅶa促进SW620细胞增殖与迁移的机制探讨  

Investigation of the mechanisms of coagulation factor Vlla-induced colon cancer SW620 cell proliferation and migration

作　　者：石文霞[1] 周红[1] 李娜[1] 黄宏亮[1] 周保成[1] 

机构地区：[1]江苏大学基础医学与医学技术学院,镇江212013

出　　处：《中华肿瘤杂志》2009年第7期485-489,共5页Chinese Journal of Oncology

基　　金：教育部回国人员科研启动基金[教外司（2003）406];江苏大学学生科研立项基金（07A142）

摘　　要：目的体外探讨凝血因子Ⅶa促进结肠癌细胞株SW620增殖与迁移的作用机制。方法采用蛋白酶激活受体2激动剂（PAR2-AP）、凝血因子Ⅶa等处理SW620细胞，以实时定量PCR检测SW620细胞中自细胞介素8（IL-8）、组织因子（TF）及半胱氨酸蛋白酶7（caspase-7）mRNA的表达水平；以酶联免疫吸附试验（ELISA）检测细胞上清IL-8蛋白的含量；以Xa生成法检测细胞TF活性；以Western blot法检测细胞磷酸化p38丝裂原活化蛋白激酶（P—p38MAPK）水平。结果PAR2-AP、凝血因子Ⅶa能够增加SW620细胞中IL-8基因和蛋白的表达，上调TFmRNA水平及活性，下调caspase-7基因表达和P-p38MAPK水平，单克隆抗TF及抗PAR2抗体均可抑制凝血因子Ⅶa的作用。结论凝血因子Ⅶa与细胞表面TF形成复合物，通过活化PAR2，上调结肠癌细胞株SW620中IL-8、TF的表达，下调细胞caspase-7表达，从而促进细胞增殖与迁移能力，p38MAPK在此过程中起负性调节作用。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 Ⅶ a were not only blocked by anti-TF but also by anti-PAR2 antibodies. Conclusion Factor Ⅶ a 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.

关 键 词：结肠肿瘤 受体 PAR2 因子Ⅶa 细胞增殖 

分 类 号：R686[医药卫生—骨科学]