Inhibition of human neuroblastoma in SCID mice by low-dose of selective Cox-2 inhibitor nimesulide.
Neuroblastoma is the most common solid tumor of infants and carries a poor prognosis especially in advanced stages. The present recommended therapies carry a high risk of side effects that is associated with long-term morbidity. We evaluated the efficacy of a low dose of the selective cyclooxygenase-2 inhibitor Nimesulide in preventing human Neuroblastoma tumor growth in Severe Combined Immune-deficient mice. Mice containing established tumors (SH-SY5Y cells) treated with 20 mg/kg Nimesulide every 4th day beginning on day 1 of cell injections resulted in a 65% reduction of tumor growth compared to the DMSO treated control mice (P<0.05) but did not significantly reduce tumor growth when Nimesulide was started once tumors reached 1 cm. There was a reduction in the level of cyclooxygenase-2 protein and induction of effecter caspases in tumors treated with Nimesulide. However, there was no change in the levels of X-Inhibitor-of-Apoptosis-Protein, Smac/Diablo, or proteins of the PI3/Akt pathway following Nimesulide treatment. In Conclusion, low doses of Nimesulide can potentially be used as a chemopreventive agent for human Neuroblastoma.
Parashar
Bhupesh
B
Department of Radiation Oncology, Montefiore Medical Center, and Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Shafit-Zagardo
Bridget
B
D000818:Animals; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D011897:Random Allocation; D013449:Sulfonamides / Q000008:administration & dosage*; D047368:Tumor Burden / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
D052246:Cyclooxygenase 2 Inhibitors; D013449:Sulfonamides; C012655:nimesulide