FOXM1-mediated downregulation of uPA and MMP9 by 3,3'-diindolylmethane inhibits migration and invasion of human colorectal cancer cells

  • Authors:
    • Hua Jin
    • Xiu Juan Li
    • Man Hee Park
    • Soo Mi Kim
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  • Published online on: April 28, 2015     https://doi.org/10.3892/or.2015.3938
  • Pages: 3171-3177
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Abstract

Although 3,3'-diindolylmethane (DIM) has been suggested to reduce the risk of colorectal cancer, the underlying biological mechanism is not clearly understood. In the present study, we investigated the effect of DIM on the migratory and invasive activities of the human colorectal cancer cell lines DLD-1 and HCT116. DIM significantly inhibited the migration and invasion of colorectal cancer cells as assessed by wound healing and Matrigel invasion assays. The migratory ability of the DLD-1 and HCT116 cells was significantly reduced by DIM at 24 and 48 h. DIM also significantly inhibited the invasion rate of the DLD-1 and HCT116 cells in a dose-dependent manner. The mRNA expression levels of urokinase type plasminogen activator (uPA) and matrix metalloprotease 9 (MMP9) were significantly attenuated, whereas expression of E-cadherin mRNA was significantly enhanced, following DIM treatment. DIM also decreased the protein levels of uPA and MMP9, yet significantly increased E-cadherin protein expression. In addition, DIM significantly reduced the mRNA and protein levels of FOXM1 in the DLD-1 and HCT116 cells. Our results suggest that DIM can influence the cell migratory and invasive properties of human colorectal cancer cells and may decrease the invasive capacity of colorectal cancer through downregulation of uPA and MMP9 mediated by suppression of the transcription factor FOXM1.
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June-2015
Volume 33 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Jin H, Li XJ, Park MH and Kim SM: FOXM1-mediated downregulation of uPA and MMP9 by 3,3'-diindolylmethane inhibits migration and invasion of human colorectal cancer cells. Oncol Rep 33: 3171-3177, 2015
APA
Jin, H., Li, X.J., Park, M.H., & Kim, S.M. (2015). FOXM1-mediated downregulation of uPA and MMP9 by 3,3'-diindolylmethane inhibits migration and invasion of human colorectal cancer cells. Oncology Reports, 33, 3171-3177. https://doi.org/10.3892/or.2015.3938
MLA
Jin, H., Li, X. J., Park, M. H., Kim, S. M."FOXM1-mediated downregulation of uPA and MMP9 by 3,3'-diindolylmethane inhibits migration and invasion of human colorectal cancer cells". Oncology Reports 33.6 (2015): 3171-3177.
Chicago
Jin, H., Li, X. J., Park, M. H., Kim, S. M."FOXM1-mediated downregulation of uPA and MMP9 by 3,3'-diindolylmethane inhibits migration and invasion of human colorectal cancer cells". Oncology Reports 33, no. 6 (2015): 3171-3177. https://doi.org/10.3892/or.2015.3938