E series prostaglandins alter the proliferative, apoptotic and migratory properties of T98G human glioma cells in vitro

Lipids in Health and Disease

Alison Colquhoun¹  Renata N Gomes¹ 

[1] Department of Cell and Developmental Biology, University of São Paulo, São Paulo, CEP 05508-900, SP, Brazil

关键词: Migration;    Apoptosis;    Ibuprofen;    Prostaglandin;    Glioma;   

Others  :  1160117
DOI  :  10.1186/1476-511X-11-171

 received in 2012-09-13, accepted in 2012-12-04,  发布年份 2012

【 摘 要 】

Background

In 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.

Methods

T98G 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.

Results

A 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).

Conclusions

The 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.

【 授权许可】

   
2012 Gomes and Colquhoun; licensee BioMed Central Ltd.

【 图 表 】

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