Study on the mechanism of IFN-γ or IL-4 in regulating tumorigenicity and cell adhesion of human breast cancer cell line MCF-7 and its mechanism
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Abstract:
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.
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Projects supported by the National Natural Science Foundation of China(No. 81273552, No. 30901985), and the Tianjin Natural Scinece Foundation (No. 15JCYBJC26000)