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Article

5-Azacytidine regulates matrix metalloproteinase-9 expression, and the migration and invasion of human fibrosarcoma HT1080 cells via PI3-kinase and ERK1/2 pathways

  • Authors:
    • Seon-Mi Yu
    • Song Ja Kim
  • View Affiliations / Copyright

    Affiliations: Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongju 32588, Republic of Korea
  • Pages: 1241-1247
    |
    Published online on: July 6, 2016
       https://doi.org/10.3892/ijo.2016.3612
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Abstract

Abnormal methylation of promoter CpG islands is one of the hallmarks of cancer cells, and is catalyzed by DNA methyltransferases. 5-azacytidine (5-aza C), a methyltransferase inhibitor, can cause demethylation of promoter regions of diverse genes. Epigenetic processes contribute to the regulation of matrix metalloproteinase (MMP) expression. However, little is known about the mechanisms and effects of 5-aza C on the invasive and migratory capacities of human fibrosarcoma HT1080 cells. In the present study, we found that 5-aza C induces MMP-9 activity, as determined by zymography. HT1080 cell proliferation was determined following 5-aza C administration by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle was examined by flow cytometry. 5-aza C treatment inhibited cell proliferation without affecting cell viability. Furthermore, 5-aza C significantly promoted migration and invasion of HT1080 cells. 5-aza C treatment enhanced phosphorylation of extracellular signal-regulated kinase (ERK) and phosphoinositide (PI)3-kinase/Akt, and their inhibitors blocked MMP-9 activity induction, and cellular invasion and migration. Together, these findings suggest that promoter methylation may be one of the mechanisms modulating MMP-9 levels in HT1080 cells, and that 5-aza C-induced MMP-9 production is associated with the activation of ERK and PI3-kinase/Akt signaling pathways.
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Copy and paste a formatted citation
Spandidos Publications style
Yu S and Kim SJ: 5-Azacytidine regulates matrix metalloproteinase-9 expression, and the migration and invasion of human fibrosarcoma HT1080 cells via PI3-kinase and ERK1/2 pathways. Int J Oncol 49: 1241-1247, 2016.
APA
Yu, S., & Kim, S.J. (2016). 5-Azacytidine regulates matrix metalloproteinase-9 expression, and the migration and invasion of human fibrosarcoma HT1080 cells via PI3-kinase and ERK1/2 pathways. International Journal of Oncology, 49, 1241-1247. https://doi.org/10.3892/ijo.2016.3612
MLA
Yu, S., Kim, S. J."5-Azacytidine regulates matrix metalloproteinase-9 expression, and the migration and invasion of human fibrosarcoma HT1080 cells via PI3-kinase and ERK1/2 pathways". International Journal of Oncology 49.3 (2016): 1241-1247.
Chicago
Yu, S., Kim, S. J."5-Azacytidine regulates matrix metalloproteinase-9 expression, and the migration and invasion of human fibrosarcoma HT1080 cells via PI3-kinase and ERK1/2 pathways". International Journal of Oncology 49, no. 3 (2016): 1241-1247. https://doi.org/10.3892/ijo.2016.3612
Copy and paste a formatted citation
x
Spandidos Publications style
Yu S and Kim SJ: 5-Azacytidine regulates matrix metalloproteinase-9 expression, and the migration and invasion of human fibrosarcoma HT1080 cells via PI3-kinase and ERK1/2 pathways. Int J Oncol 49: 1241-1247, 2016.
APA
Yu, S., & Kim, S.J. (2016). 5-Azacytidine regulates matrix metalloproteinase-9 expression, and the migration and invasion of human fibrosarcoma HT1080 cells via PI3-kinase and ERK1/2 pathways. International Journal of Oncology, 49, 1241-1247. https://doi.org/10.3892/ijo.2016.3612
MLA
Yu, S., Kim, S. J."5-Azacytidine regulates matrix metalloproteinase-9 expression, and the migration and invasion of human fibrosarcoma HT1080 cells via PI3-kinase and ERK1/2 pathways". International Journal of Oncology 49.3 (2016): 1241-1247.
Chicago
Yu, S., Kim, S. J."5-Azacytidine regulates matrix metalloproteinase-9 expression, and the migration and invasion of human fibrosarcoma HT1080 cells via PI3-kinase and ERK1/2 pathways". International Journal of Oncology 49, no. 3 (2016): 1241-1247. https://doi.org/10.3892/ijo.2016.3612
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