Laboratory Investigation

Journal of Neuro-Oncology

, Volume 78, Issue 2, pp 129-134

First online:

Inhibition of human Neuroblastoma in SCID mice by low-dose of selective Cox-2 inhibitor Nimesulide

  • Bhupesh ParasharAffiliated withDepartment of Radiation Oncology, Montefiore Medical Center
  • , Bridget Shafit-ZagardoAffiliated withDepartment of Pathology, Albert Einstein College of MedicineDepartment of Radiation Oncology, Weill Cornell Medical Center,, New York Presbyterian Hospital Email author 

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Summary

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 1cm. 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.

Keywords

Cox-2 Neuroblastoma Nimesulide SCID XIAP