Cyclooxygenase Inhibition Alters Proliferative, Migratory, and Invasive Properties of Human Glioblastoma Cells In Vitro

Author(s)

Ferreira, Matthew Thomas ; Miyake, Juliano Andreoli ; Gomes, Renata Nascimento ; Feitoza, Fabio ; Stevannato, Pollyana Bulgarelli ; da Cunha, Andrew Silva ; Serachi, Fernanda de Oliveira ; Panagopoulos, Alexandros Theodoros ; Colquhoun, Alison

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 9, p. 23-pg., 2021-05-01.

Abstract

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. (AU)

• FAPESP's process: 15/08777-0 - Eicosanoids and the biology of gliomas: influence upon cell proliferation and migration and the response to chemotherapeutic drugs
• Grantee: Alison Colquhoun
• Support Opportunities: Regular Research Grants