The cyclooxygenase inhibitor indomethacin modulates gene expression and represses the extracellular matrix protein laminin γ1 in human glioblastoma cells

• Published in: Experimental cell research Vol. 302; no. 2; pp. 244 - 252
• Main Authors: Ishibashi, Minako, Bottone, Frank G., Taniura, Seijiro, Kamitani, Hideki, Watanabe, Takashi, Eling, Thomas E.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.01.2005
• Subjects: COX; Cyclooxygenase; Glioblastoma; Invasion; Laminin γ1; Nonsteroidal anti-inflammatory drug; NSAID; Cyclooxygenase; Laminin γ1; NSAID; Nonsteroidal anti-inflammatory drug; Glioblastoma; COX; Invasion
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2004.09.021

The induction of cyclooxygenase-2 (COX-2) expression is associated with more aggressive gliomas and poor survival. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit COX activity and have antitumorigenic properties. In this report, our initial aim was to determine if indomethacin would alter gene expression as measured by suppression subtractive hybridization (SSH). Three up-regulated and four down-regulated genes by indomethacin treatment were identified. Laminin γ1, an extracellular matrix molecule, was the most significantly repressed gene. The repression of laminin γ1 by indomethacin was confirmed by Northern and Western blot analyses and occurred in a concentration- and time-dependent manner at the protein level. Among several NSAIDs tested, only sulindac sulfide and indomethacin suppressed laminin γ1 protein expression, and this repression was observed in both COX-expressing and -deficient cell lines, suggesting that laminin γ1 repression by COX inhibitors was independent of COX. Indomethacin, at a concentration that represses laminin γ1, inhibited glioblastoma cell invasion that was partially restored with additional human laminin protein containing γ1 chain. The repression of laminin γ1 by NSAIDs may be related to attenuation of invasion of brain tumors. These findings are important in understanding the chemopreventive activity of some NSAIDs and could be relevant for designing therapeutic strategies against glioblastoma.