Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/ijms22094297
Keywords
cyclooxygenase; prostaglandin; glioblastoma; matrix metalloproteinase; migration
Funding
- FAPESP [2010/5199-0, 2015/08777-0]
- Coordenacao de Aperfeicoamento Pessoal de Nivel Superior-Brazil (CAPES) [001]
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The study demonstrated the importance of PGE(2) signaling through the EP2 and EP4 receptors in controlling GBM cell biology, as well as a relationship between COX1 and MMP2 in these cells. These findings suggest a potential novel therapeutic target for drug development.
Prostaglandin E-2 (PGE(2)) is known to increase glioblastoma (GBM) cell proliferation and migration while cyclooxygenase (COX) inhibition decreases proliferation and migration. The present study investigated the effects of COX inhibitors and PGE(2) receptor antagonists on GBM cell biology. Cells were grown with inhibitors and dose response, viable cell counting, flow cytometry, cell migration, gene expression, Western blotting, and gelatin zymography studies were performed. The stimulatory effects of PGE(2) and the inhibitory effects of ibuprofen (IBP) were confirmed in GBM cells. The EP2 and EP4 receptors were identified as important mediators of the actions of PGE(2) in GBM cells. The concomitant inhibition of EP2 and EP4 caused a significant decrease in cell migration which was not reverted by exogenous PGE(2). In T98G cells exogenous PGE(2) increased latent MMP2 gelatinolytic activity. The inhibition of COX1 or COX2 caused significant alterations in MMP2 expression and gelatinolytic activity in GBM cells. These findings provide further evidence for the importance of PGE(2) signalling through the EP2 and the EP4 receptor in the control of GBM cell biology. They also support the hypothesis that a relationship exists between COX1 and MMP2 in GBM cells which merits further investigation as a novel therapeutic target for drug development.
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