TGF-β通过激活smad2信号通路上调CXCR4表达促进非小细胞肺癌A549细胞迁移和侵袭-现代医学

TGF-β通过激活smad2信号通路上调CXCR4表达促进非小细胞肺癌A549细胞迁移和侵袭

单位：西安医学院第二附属医院心胸外科, 陕西西安 710038

分类号：R734.2

出版年·卷·期（页码）：2019·47·第五期（555-560）

摘要：

目的：探索TGF-β是否能够通过上调超化因子受体4（CXCR4）的表达而促进非小细胞肺癌的迁移和侵袭，并证实该效应是否与smad2信号相关。方法：常规培养肺癌A549细胞后，通过Transwell迁移小室观察10 ng·ml^-1的TGF-β对肺癌细胞迁移和侵袭能力影响。通过蛋白印迹和qPCR法检测10 ng·ml^-1的TGF-β处理细胞后CXCR4的表达情况，采取蛋白印迹法检测smad2激活情况。使用TGF-β/smad信号通路抑制剂LY2109761，检测CXCR4的表达以及肺癌细胞迁移和侵袭能力。结果：10 ng·ml^-1的TGF-β显著提升肺癌A549细胞迁移和侵袭能力（P<0.05），同时10 ng·ml^-1的TGF-β处理后显著提升CXCR4的表达水平和smad2的活化水平（P<0.05）。使用smad信号通路抑制剂LY2109761作用后，细胞CXCR4的表达水平和smad2的活化水平显著降低（P<0.05）。结论：TGF-β能够通过上调CXCR4的表达而促进非小细胞肺癌的迁移和侵袭，该效应可能与TGF-β激活了smad2信号相关。

Objective:To explore whether TGF-β can promote the migration and invasion of non-small cell lung cancer by up-regulating the expression of CXCR4 and confirm whether this effect is associated with smad2 signaling. Methods:After cultured lung cancer A549 cells, the effect of 10 ng·ml^-1 TGF-β on the migration and invasion of lung cancer cells was observed by Transwell migration chamber. The expression of CXCR4 was detected by Western blotting and qPCR method after 10 ng·ml^-1 of TGF-β-treated cells. The activation of smad2 was detected by Western blotting. The expression of CXCR4 and the migration and invasion ability of lung cancer cells were examined by usingTGF-β/smad signaling pathway inhibitor LY2109761. Results:10 ng·ml^-1 of TGF-β significantly increased the migration and invasion of lung cancer A549 cells. At the same time, 10 ng·ml^-1 TGF-β treatment significantly increased the expression level of CXCR4 and the activation level of smad2. After treatment with the smad signaling pathway inhibitor LY2109761, the expression level of CXCR4 and the ability to migrate and invade were significantly reduced. Conclusion:TGF-β can promote the migration and invasion of non-small cell lung cancer by up-regulating the expression of CXCR4, which may be related to the activation of smad2 signaling by TGF-β.

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