Journal of Neuro-Oncology

, Volume 72, Issue 1, pp 1–9 | Cite as

Inhibition of cell invasion by indomethacin on glioma cell lines: in vitro study

  • Maode Wang
  • Daizo Yoshida
  • Shouxun Liu
  • Akira Teramoto
Laboratory Investigation


Malignant glioma invasion into the surrounding brain tissue is still a major problem for any therapeutical methods. Matrix metalloproteinases (MMPs) have been implicated as important factors in this pathological process. In this study, one of the non-steroidal anti-inflammatory drugs (NSAIDs) indomethacin was employed to investigate the effect of inhibition of cell invasion mediated by MMP-2 and MMP-9 in human malignant glioma cell lines, A172, U87MG, U251MG, and U373MG in vitro. MTT assay was firstly examined to determine non-cytotoxic dose range, then gelatin zymography, matrigel invasion assay, migration assay and MMP-2 activity assay for 24 h exposure in indomethacin were employed to assess the inhibitory effect of indomethacin. MTT assay revealed that dose with 0, 50, and 500 μM/ml were non-cytotoxic. Zymography demonstrated: (a) expression of MMP-2 and MMP-9 activity was downregulated along with elevated dose of indomethacin. (b) MMP-2 activity that changed from pro-MMP-2 to active form of MMP-2 in supernatants of cell lines could not be inhibited by indomethacin. Invasion assay disclosed that the number of invading cells through the matrigel were significantly decreased in a dose dependent manner. Migration assay indicated indomethacin did not affect cells migration. MMP-2 activity assay showed the total and active MMP-2 secretion was suppressed by 500 μM/ml of indomethacin. Our present study is the first report on inhibitive effect of indomethacin mediated by MMP-2 and MMP-9 in invasion assay of glioma cell lines. The current study suggested that non-cytotoxic level of indomethacin was able to reduce the cell invasion of malignant gliomas mediated by MMP-2 and MMP-9, but it did not affected on cell motility. It also lowered down the activity of MMP-2 and MMP-9, and could reduce of MMP-2 secretion of cell lines. Thus, high concentration of indomethacin within non-cytotoxic dose might offer a new therapeutic strategy to impair cell invasion of gliomas.


active assay cell invasion cell migration glioma indomethacin matrix metalloproteinase zymogragh 


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Copyright information

© Springer 2005

Authors and Affiliations

  • Maode Wang
    • 1
  • Daizo Yoshida
    • 2
  • Shouxun Liu
    • 1
  • Akira Teramoto
    • 2
  1. 1.Department of Neurosurgery, The First HospitalXi’an Jiaotong UniversityXi’anChina
  2. 2.Department of NeurosurgeryNippon Medical SchoolTokyoJapan

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