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-2 proteins. Conclusion: Biologic axis of CXCL12/CXCR4 could up-regulate the expressions of Survivin and MMP-2 proteins through activation of ERK pathway, 〖JP3〗thus inspire a series of biological effects in proliferation and invasion of the Ishikawa cell.

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）