EXTH-72. CELECOXIB INHIBITS PROLIFERATION AND INDUCES APOPTOSIS IN GLIOMA STEM CELLS AND AN ANIMAL MODEL OF GLIOBLASTOMA

Biological characteristics of glioblastoma multiforme (GBM), such as resistance to chemo- and radiotherapy and their infiltrative and proliferative nature, suggest that these tumors contain cancer stem cells. However, there are few reports of drug treatments for gliomas that specifically target stem cells. Cyclooxygenase (COX)-2 overexpression is associated with increased angiogenesis, tumor invasion, and the development of tumor cell resistance to apoptosis. Celecoxib is a selective COX-2 inhibitor that has shown anti-neoplastic activity in several malignancies, but this has not been investigated in glioma stem cells (GSCs). We addressed this in the present study by examining the effect of celecoxib on GSCs derived from neural stem cells. Celecoxib induced apoptosis and inhibited proliferation in GSCs. In an orthotopic animal model of GBM, celecoxib suppressed tumor growth, prolonged survival, and reduced the expression levels of C-C motif chemokine ligand 2 and C-X-C motif chemokine ligand 10, which are associated with monocyte infiltration and cell proliferation, respectively. These results provide evidence for the anti-neoplastic activity of celecoxib in GSCs and suggest that it can be effective for the treatment of GBM.