Overexpression of S100A9 in human glioma and in-vitro inhibition by aspirin.

Our previous work has shown that S100A9 promotes the growth of glioma cells. The aim of this study was to investigate S100A9 expression in glioma cells and to explore the potential of NSAIDs in the inhibition of S100A9. The levels of S100A9 were analyzed in five normal human brain tissues and 109 astrocytomas by immunohistochemical analysis. In addition, S100A9 levels were detected in normal human astrocytes, glioma cell lines, and six pairs of matched astrocytoma tissues by reverse transcription-PCR or western blotting analysis. After treatment with 4, 8, and 16 mmol/l aspirin, cell viability, early apoptosis rate, and S100A9 levels were quantified. Cell viability and the changes in S100A9 levels were also examined in glioma cells exposed to a cyclooxygenase-2 inhibitor, NS-398, alone and in combination with prostaglandin E2. We found that S100A9 was upregulated in astrocytomas and was significantly (P<0.05) correlated with histologic grades. S100A9 protein levels were also elevated in six astrocytomas compared with matched adjacent noncancerous tissues. Both S100A9 mRNA and protein levels were higher in glioma cell lines than in normal human astrocytes (P<0.05). Aspirin treatment inhibited cell proliferation and caused early apoptosis in glioma, coupled with reduced S100A9 levels. Treatment with NS-398 decreased cell growth and expression of S100A9 in glioma cells; these effects were partially reversed by exogenous prostaglandin E2. These results suggest overexpression of S100A9 in glioma cells. Aspirin may be a novel candidate for targeted prevention of S100A9 overexpression in glioma cells.