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


Al Musella's Comments: (This is his personal views and are not necessarily the views of the Musella Foundation!)



Website: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15803368&dopt=Abstract

Posted on: 04/06/2005

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

J Neurooncol. 2005 Mar;72(1):1-9.

Wang M, Yoshida D, Liu S, Teramoto A.

Department of Neurosurgery, The First Hospital, Xi'an Jiaotong University, No.1 Jiankang Road, Xi'an, China, 710061, maodewang@yahoo.com.cn.

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 muM/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 muM/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.

PMID: 15803368 [PubMed - as supplied by publisher]



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