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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 被引量:5

Role of ERK transduction signaling pathway in proliferation and invasion of endometrial carcinoma cells promoted by CXCL12
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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.
作者 马营营 黄煜 颜莉莉 叶元英 刘萍萍 MA Yingying, HUANG Yu, YAN Lili, YE Yuanying, LIU Pingping ( Department of Gynecology, Affiliated Hospital of Qingdao University,Qingdao 266010, Shandong, China)
出处 《中国肿瘤生物治疗杂志》 CAS CSCD 北大核心 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)
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 chemokine CXCL12 endometrial carcinoma extracellular signal-regulated kinase 1 /2 Survivin protein MMP-2 protein
作者简介 马营营(1987-),女,山东省济宁市人,硕士生,主要从事妇科肿瘤基础和临床研究,E-mail:linchuangmy@163.com 黄煜(HUANGYu,correspondingauthor),E—mail:huangyuqd@126.com
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