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标题:Metformin inhibits the invasion of human hepatocellular carcinoma cells and enhances the chemosensitivity to sorafenib through a downregulation of the ERK/JNK-mediated NF-κB-dependent pathway that reduces uPA and MMP-9 expression.
时间:2019-03-15 13:43:37
DOI:10.1007/s00726-014-1838-4
PMID:25245054
作者:Shu-Ching Hsieh;Jen-Pi Tsai;Shun-Fa Yang;Meng-Ju Tang;Yi-Hsien Hsieh
出版源: 《Amino Acids》 ,2014 ,46 (12) :2809-2822
摘要:Metformin inhibits the invasion of human hepatocellular carcinoma cells and enhances the chemosensitivity to sorafenib through a downregulation of the ERK/JNK-...
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页数:15 PAGES
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目录:
  • Metformin inhibits the invasion of human hepatocellular carcinoma cells and enhances the chemosensitivity to sorafenib through a downregulation of the ERKJNK-mediated NF-κB-dependent pathway that reduces uPA and MMP-9 expression
    • Abstract
    • Introduction
    • Materials and methods
      • Reagents
      • Cell culture
      • Cell proliferation assay
      • Migration and invasion assay
      • Analysis of MMP-9 and uPA activities (zymography assay)
      • Immunofluorescence staining
      • Western blotting
      • RNA extraction and quantification reverse transcriptase-polymerase chain reaction (qRT-PCR)
      • Preparation of cell lysate and nucleus fraction
      • Luciferase assay
      • Chromatin immunoprecipitation (ChIP) assay
      • Statistical analysis
    • Results
      • Metformin decreased cell migration and invasion in three HCC cells
      • Metformin inhibits MMP-9 and uPA activity, expression, and mRNA levels in HCC cells
      • Metformin inhibits the phosphorylation of ERK12 and JNK12 in HCC cells
      • Metformin inhibits the transcriptional activity of MMP-9 and uPA by disrupting nuclear translocation and activity of NF-κB
      • Combination of metformin and sorafenib inhibits HCC cell invasion through inhibition of ERK12 and JNK12 activation
      • Combination treatment inhibited nuclear translocation and binding activities of NF-κB dependent on MMP-9 and uPA expression
    • Discussion
    • Acknowledgments
    • References

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