Abstract
BackgroundIn many types of cancer, prostaglandin E2 (PGE2) is associated with tumour related processes including proliferation, migration, angiogenesis and apoptosis. However in gliomas the role of this prostanoid is poorly understood. Here, we report on the proliferative, migratory, and apoptotic effects of PGE1, PGE2 and Ibuprofen (IBP) observed in the T98G human glioma cell line in vitro.MethodsT98G human glioma cells were treated with IBP, PGE1 or PGE2 at varying concentrations for 24–72 hours. Cell proliferation, mitotic index and apoptotic index were determined for each treatment. Caspase-9 and caspase-3 activity was measured using fluorescent probes in live cells (FITC-LEHD-FMK and FITC-DEVD-FMK respectively). The migratory capacity of the cells was quantified using a scratch migration assay and a transwell migration assay.ResultsA significant decrease was seen in cell number (54%) in the presence of 50 μM IBP. Mitotic index and bromodeoxyuridine (BrdU) incorporation were also decreased 57% and 65%, respectively, by IBP. The apoptotic index was increased (167%) and the in situ activity of caspase-9 and caspase-3 was evident in IBP treated cells. The inhibition of COX activity by IBP also caused a significant inhibition of cell migration in the monolayer scratch assay (74%) and the transwell migration assay (36%).In contrast, the presence of exogenous PGE1 or PGE2 caused significant increases in cell number (37% PGE1 and 45% PGE2). When mitotic index was measured no change was found for either PG treatment. However, the BrdU incorporation rate was significantly increased by PGE1 (62%) and to a greater extent by PGE2 (100%). The apoptotic index was unchanged by exogenous PGs. The addition of exogenous PGs caused an increase in cell migration in the monolayer scratch assay (43% PGE1 and 44% PGE2) and the transwell migration assay (28% PGE1 and 68% PGE2).ConclusionsThe present study demonstrated that treatments which alter PGE1 and PGE2 metabolism influence the proliferative and apoptotic indices of T98G glioma cells. The migratory capacity of the cells was also significantly affected by the change in prostaglandin metabolism. Modifying PG metabolism remains an interesting target for future studies in gliomas.
Highlights
In many types of cancer, prostaglandin E2 (PGE2) is associated with tumour related processes including proliferation, migration, angiogenesis and apoptosis
Glioblastoma multiforme (GBM) are characterized by genetic alterations affecting genes that control cell growth, migration, apoptosis, and invasion
Clinical trials have demonstrated that longterm Non-steroidal anti-inflammatory drugs (NSAIDs) use significantly reduces the risk of colorectal cancer and other tumours such as breast, lung, prostate and gastric cancer [3,4,5]
Summary
In many types of cancer, prostaglandin E2 (PGE2) is associated with tumour related processes including proliferation, migration, angiogenesis and apoptosis. We report on the proliferative, migratory, and apoptotic effects of PGE1, PGE2 and Ibuprofen (IBP) observed in the T98G human glioma cell line in vitro. Malignant gliomas and especially Glioblastoma multiforme (GBM) are the most malignant and prevalent intracranial tumours, classified as grade IV by the World Health Organization (WHO). GBMs are characterized by genetic alterations affecting genes that control cell growth, migration, apoptosis, and invasion. Despite very aggressive treatment including surgery and combined radio and chemotherapy the median survival for most patients with GBM is only 1 year. Clinical trials have demonstrated that longterm NSAID use significantly reduces the risk of colorectal cancer and other tumours such as breast, lung, prostate and gastric cancer [3,4,5]
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