摘要
目的:纤溶酶原激活物抑制剂1(PAI-1)在凝血、创伤修复、炎症和肿瘤转移中起重要作用。已有报道转化生长因子β1(TGF-β1)能通过Smad通路诱导PAI-1表达,但TGF-β1能否通过激活非Smad通路诱导PAI-1表达尚不清楚,因此本研究探讨了在卵巢癌细胞中TGF-β1激活的非Smad通路p38丝裂原活化蛋白激酶(p38MAPK)和细胞外信号调节激酶(ERK)与TGF-β1上调PAI-1表达的关系。方法:用10μg/L TGF-β1处理卵巢癌SKOV3细胞和HO-8910细胞后,采用real-time PCR和Western blotting的方法检测PAI-1的表达,用磷酸化p38MAPK的抗体和磷酸化ERK的抗体检测p38 MAPK和ERK的激活情况,用p38 MAPK和ERK的特异性抑制剂SB203580和PD98059分别抑制其活性后,检测PAI-1的表达。结果:TGF-β1在卵巢癌细胞中可明显上调PAI-1mRNA和蛋白的表达,并可快速激活p38 MAPK和ERK。用p38 MAPK的抑制剂可以明显抑制TGF-β1上调PAI-1表达,但是抑制ERK活性对TGF-β1上调PAI-1表达没有明显影响。结论:TGF-β1激活的p38 MAPK通路参与了TGF-β1上调PAI-1的表达。
AIM： To investigate the relationship between up-regulation of plasminogen activator inhibitor-1（ PAI-1） expression and activation of p38 mitogen-activated protein kinase（ p38 MAPK） and extracellular signal-regulated kinase（ ERK） pathways by TGF-β1 in human ovarian cancer cells. METHODS： PAI-1 expression in human ovarian cancer cells treated with TGF-β1（ 10 μg / L） was assayed by real-time PCR and Western blotting. The activation of p38 MAPK and ERK was determined by Western blotting using phosphorylated p38 MAPK and phosphorylated ERK antibodies.Specific p38 MAPK inhibitor（ SB203580） or ERK inhibitor（ PD98059） was used to inhibit their activation. RESULTS：TGF-β1 up-regulated the expression of PAI-1,and activated p38 MAPK and ERK pathways in the ovarian cancer cells. Inhibition of p38 MAPK activation by SB203580 resulted in significant inhibition of the mRNA expression of PAI-1 induced by TGF-β1. However,inhibition of ERK activation did not significantly alter TGF-β1-induced increase in PAI-1 mRNA level. CONCLUSION： TGF-β1-activated p38 MAPK pathway contributes to the up-regulation of PAI-1 expression by TGF-β1 in ovarian cancer cells.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2015年第2期284-288,共5页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.31301164)
