Abstract
Prostaglandin E2 (PGE2) 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 PGE2 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 PGE2 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 PGE2 in GBM cells. The concomitant inhibition of EP2 and EP4 caused a significant decrease in cell migration which was not reverted by exogenous PGE2. In T98G cells exogenous PGE2 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 PGE2 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.
Highlights
Primary brain tumors are estimated to be responsible for almost 2.5% of all cancer related deaths
In this study we examined the influence of COX1 and COX2 inhibition upon cell proliferation and migration, and matrix metalloproteinase 2 (MMP2), MMP9 and matrix metalloproteinase 14 (MMP14) expression in GBM cell lines in vitro
The present study has confirmed the positive effects of Prostaglandin E2 (PGE2) on cell proliferation and the inhibitory effects of the Nonsteroidal anti-inflammatory drugs (NSAIDs), IBP as previously seen for other GBM cell lines [8,21,22]
Summary
Primary brain tumors are estimated to be responsible for almost 2.5% of all cancer related deaths. Astrocytic tumors including pilocytic astrocytoma, anaplastic astrocytoma, diffuse astrocytoma and glioblastomas (GBM) account for 76.4% of all gliomas. Of these astrocytic gliomas, GBMs account for 57.3%. The gliomas are by far the most common primary brain tumors, with a mortality rate higher than any other brain related disease except for brain related vascular problems, and patients with GBM have a dismal prognosis with a five-year overall survival rate of 6.8% [1]. Despite the efforts to treat GBM patients using the conventional therapies of surgical resection, radiation therapy and chemotherapy, the efficacy of these combined treatments is short-lived and the overall survival for most patients is between 12 and 15 months
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