Primitive neuroectodermal tumours (PNET)/Medulloblastoma (MB) is the most common malignant childhood tumour of CNS and the second most important tumour of childhood in terms of annual deaths. Cyclooxygenases (COX) catalyse the conversion of arachidonic acid to prostaglandin’s. COX-2 is up-regulated in several adult epithelial cancers and is linked to proliferation and resistance to apoptosis. We detected COX-2 expression in 40 out of 41 investigated MB primary tumours of different clinical subsets as well as in all MB cell lines investigated. Treatment of MB cell lines with the selective COX-2 inhibitor, celeCOXib, or the dual COX-1/COX2 inhibitor, diclofenac, resulted in dose-dependent growth inhibition and reduction of clonogenic formation of MB cell lines. COX inhibitor-induced cell death was characterized by a change in the mitochondrial transmembrane potential followed by a cleaveage of caspase-3, -9 and PARP. FACS analysis revealed accumulation of cells in sub G1 as well as Annexin V positive staining in MB cells treated with COX inhibitors. These data indicate the potential use of COX inhibitors as a treatment option for children with PNET/medulloblastoma.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]