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TGF-β1可通过ERK信号通路调节胃癌细胞MMP-2和MMP-9的表达

TGFβ1 Upregulates Expression of MMP-2 and MMP-9 through ERK Signaling Pathway in Gastric Carcinoma Cells

  • 摘要: 目的 探讨转化生长因子-β1(TGF-β1)/丝裂原活化的蛋白激酶(MAPK)通路在调节胃癌细胞MMP-2和MMP-9表达中的作用。方法 以MKN45和BGC823胃癌细胞系为研究对象。明胶酶谱法检测TGF-β1对各细胞MMP-2和MMP-9表达的影响,Western蛋白印迹检测在TGF-β1作用下各细胞中MAPK(P38、JNK、ERK)的活化情况。用相应MAPK通路的特异抑制剂对TGF-β1调节各细胞MMP-2和MMP-9的表达进行阻断研究。结果 TGF-β1可上调MKN45和BGC823细胞MMP-2和MMP-9的表达;TGF-β1可诱导BGC823细胞P38、MKN45和BGC823细胞ERK及JNK的活化;ERK特异抑制剂PD98059可明显抑制TGF-β1诱导MKN45和BGC823细胞MMP-2和MMP-9的表达,但P38特异抑制剂SB203580和JNK特异抑制剂SP600125对TGF-β1诱导这两种细胞MMP-2和MMP-9的表达无明显影响。结论 TGF-β1可通过活化ERK信号通路上调MKN45和BGC823胃癌细胞 MMP-2和MMP-9的表达。

     

    Abstract: Objective To investigate the role of TGFβ1/ MAPK signaling pathways in the regulation of MMP-2 and MMP-9 in gastric carcinoma cells. Methods MKN45 and BGC823 gastric carcinoma cell lines were used in this study. The expression of MMP-2 and MMP-9 in the two gastric carcinoma cell lines stimulated by TGFβ1 was tested by Gelatin Zymography. The activity of MAPK signaling pathway in TGFβ1-stimulated cells was measured by Western blotting. The effects of the MAPK pathway specific inhibitors on TGFβ1-activated MMP-2 and MMP-9 expression in two cell lines were examined. Results TGF-β1 induced expression of MMP-2 and MMP-9 in MKN45 and BGC823 cells. P38 was activated in BGC823 cells by TGF-β, whereas NK and ERK was activated in both MKN45 and BGC823 cells. PD98059, a ERK specific inhibitor, significantly inhibited the production of MMP-2 and MMP-9 by TGF-β1 in both MKN45 and BGC823 cells, however, SB203580 and SP600125, specific blocker for P38 and JNK, showed no effect on the MMP-2 and MMP-9 expression in both two cells. Conclusion TGF-β1 induced enhanced MMP-2 and MMP-9 expression mediated by ERK signaling pathway in MKN45 and BGC823 gastric carcinoma cell lines.

     

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