Overexpression of cyclooxygenase-2 (COX-2) in human primitive neuroectodermal tumors: effect of celecoxib and rofecoxib.
In this study the role of cyclooxygenase-2 (COX-2) in primitive neuroectodermal tumor (PNET) the most malignant brain tumors of childhood was investigated. COX-2 expression in human brain tumor biopsy samples (seven/seven) was about 6-8-fold higher than normal brain tissue and several PNET cell lines also express COX-2. The effect of selective COX-2 inhibitors, celecoxib and rofecoxib on the growth of two PNET cell lines (DAOY and PFSK) was determined. Celecoxib was more potent than rofecoxib in suppressing cell growth. Growth inhibition by celecoxib and rofecoxib was independent of Bcl-2 expression. Celecoxib suppressed the expression of Akt and activated the caspase-3 in DAOY and PFSK, whereas rofecoxib did not have such an effect.
Patti
Ratnakar
R
Division of Neuro-Oncology, Joseph Stokes Research Institute #515G, 3516 Civic Center Blvd, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Gumired
Kiranmai
K
Reddanna
Pallu
P
Sutton
Leslie N
LN
Phillips
Peter C
PC
Reddy
C Damodar
CD
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis*; D007783:Lactones / Q000494:pharmacology*; D008565:Membrane Proteins; D018242:Neuroectodermal Tumors, Primitive / Q000188:drug therapy* / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011720:Pyrazoles; D013449:Sulfonamides / Q000494:pharmacology*; D013450:Sulfones; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000068579:Celecoxib