目的：探讨Th1类细胞因子IFN-γ和Th2类细胞因子IL-4对MCF-7细胞的成瘤、黏附能力的调节作用及其相关机制。方法：常规体外培养人乳腺癌细胞系MCF-7。以前期工作中筛选出的以有效剂量rhIFN-γ（100 ng/ml）或rhIL-4（10 ng/ml）或细胞因子稀释液分别处理细胞96 h后，应用半定量RT-PCR法、Western blotting技术、双层软琼脂集落形成实验、细胞体外黏附实验等观察IFN-γ和IL-4对细胞VEGF表达、致瘤性和黏附侵袭特性的影响，并对其相关信号通路机制进行分析。结果： IFN-γ或IL-4可分别抑制或促进人乳腺癌细胞MCF-7的成瘤和黏附能力。分子机制研究表明，与对照组相比，rhIFN-γ可抑制MCF-7细胞VEGF、MMP-9的基因转录和蛋白表达水平，抑制Raf/MEK/ERK信号通路；rhIL-4可促进MCF-7细胞的VEGF、MMP-2和MMP-9的基因转录和蛋白表达水平，促进PI3K/AKT、Raf/MEK/ERK 信号通路激活。结论： 肿瘤微环境中，IFN-γ和IL-4可分别抑制和促进人乳腺癌细胞系MCF-7的VEGF表达和体外成瘤、黏附能力，其机制可能与PI3K/AKT、Raf/MEK/ERK 信号通路相关。

Objective:To study whether and how Th1-type cytokine IFN-γ and Th2-type cytokine IL-4 regulating tumorigenicity and adhesion of human breast cancer cells. Methods: Human breast cancer MCF-7 cells were treated with rhIFN-γ at 100 ng/ml or rhIL-4 at 10 ng/ml. At 96 hours after treatment, VEGF mRNA and protein levels were determined by semi-quantitative RT-PCR and Western blotting analysis, tumorigenicity by double layer soft-agar colony formation test and cell adhesion by matrigel adhesion assay respectively.Results: IFN-γ inhibited while IL-4 enhanced significantly tumorigenic and adhesive activities of MCF-7 cells. Compared with the control, rhIFN-γ significantly decreased mRNA and protein levels of VEGF and MMP-9 and down-regulated the Raf/MEK/ERK signaling pathway. On the contrary, rhIL-4 significantly increased mRNA and protein levels of VEGF, MMP-2 and MMP-9 and up-regulated the PI3K/AKT and Raf/MEK/ERK signaling pathways. Conclusion：IFN-γ and IL-4 may regulate human breast cancer cell adhesion and tumorigenicity, at least partially, through regulation of PI3K/AKT and Raf/MEK/ERK signal pathways.

国家自然科学基金资助项目（No. 81273552，No.30901985）；天津市自然科学基金资助项目 （No.15JCYBJC26000)