ERK信号转导通路在CXCL12促进子宫内膜癌细胞增殖和侵袭中的作用  

Role of ERK transduction signaling pathway in proliferation and invasion of endometrial carcinoma cells promoted by CXCL12

作　　者：马营营[1] 黄煜[1] 颜莉莉[1] 叶元英[1] 刘萍萍[1] 

机构地区：[1]青岛大学附属医院妇科,山东青岛266010

出　　处：《中国肿瘤生物治疗杂志》2016年第2期250-254,共5页Chinese Journal of Cancer Biotherapy

基　　金：山东省优秀中青年科学家科研奖励基金资助项目(No.BS2009SW002);山东省自然科学基金资助项目(No.ZR2013HM012)~~

摘　　要：目的:探讨趋化因子CXCL12及其受体CXCR4(CXCL12/CXCR4)生物学轴通过细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)信号转导通路发挥促子宫内膜癌细胞增殖和侵袭的作用。方法:应用外源性CXCL12处理子宫内膜癌Ishikawa细胞株,通过Western blotting检测不同时间位点ERK1/2的磷酸化水平和Survivin蛋白的表达;通过ELISA检测细胞培养上清液中MMP-2的分泌水平。同时分析AMD3100和PD98059对细胞ERK1/2磷酸化水平、Survivin蛋白水平和MMP-2分泌水平的影响。结果:外源性CXCL12刺激后,可迅速上调ERK1/2的磷酸化水平(t=0.887,P<0.01),促进Survivin蛋白和MMP-2蛋白的表达(t=0.861,P<0.01;t=0.297,P<0.01),且三者均呈时间依赖性。PD98059和AMD3100均能明显抑制外源性CXCL12诱导后ERK1/2的磷酸化水平,而且在两者共同作用下,能完全抑制ERK1/2的磷酸化水平,阻断ERK通路的激活,下调Survivin蛋白和MMP-2蛋白的表达。结论:CXCL12/CXCR4生物学轴通过激活ERK通路上调Survivin蛋白和MMP-2蛋白表达,从而引发Ishikawa细胞一系列增殖和侵袭的生物学效应。Objective： To explore the role of chemokine CXCL12 and its receptor CXCR4（ biologic axis CXCL12/CXCR4） in promoting proliferation and invasion of endometrial carcinoma cells through transduction signaling pathway of extracellular signal-regulated kinase（ ERK）. Methods： Ishikawa endometrial carcinoma cell line was treated with exogenous CXCL12. The phosphorylation of ERK1 /2 and the expression of survivin protein at different time points were detected by Western blotting; and secretion level of MMP-2 in supernatant of cell culture was measured by ELISA. At the same time,effects of AMD3100 and PD98059 on phosphorylation level of ERK1 /2,level of Survivin protein and secretion level of MMP-2 were analyzed. Results： After treatment with exogenous CXCL12,phosphorylation level of ERK1 /2 was rapidly risen（ t =0. 887,P〈0. 01） as well as expressions of Survivin and MMP-2 proteins were boosted（ t = 0. 861,P〈0. 01; t = 0. 297,P〈0. 01） in a time dependent manner. Both of PD98059 and AMD3100 could significantly inhibit the phosphorylation level of p-ERK after induction with exogenous CXCL12. Combined action of PD98059 and AMD3100 could completely inhibit phosphorylation of ERK,block the activation of ERK pathway,and down-regulate the expressions of Survivin and MMP-2proteins. Conclusion： Biologic axis of CXCL12 / CXCR4 could up-regulate the expressions of Survivin and MMP-2 proteins through activation of ERK pathway,thus inspire a series of biological effects in proliferation and invasion of the Ishikawa cell.

关 键 词：趋化因子CXCL12 子宫内膜癌 细胞外信号调节激酶1/2 SURVIVIN蛋白 MMP-2蛋白 

分 类 号：R739.41[医药卫生—肿瘤]