IGF-I Receptor Inhibition Combined with Rapamycin or Temsirolimus Inhibits Neuroblastoma Cell Growth

Abstract

Background: Neuroblastoma is the third most common solid tumor in children. Treatment continues to be challenging. The pathogenesis of neuroblastoma has been related to expression of the type 1 insulin-like growth factor receptor (IGF1R) and to transcription factor MYC-N amplification. Previous studies have shown that MYC-N expression is disrupted by blockade of the IGF1R with a specific monoclonal antibody, αIR3. Inhibition of IGF1R signaling can be accomplished by other agents, including rapamycin or temsirolimus, which target mTOR (mammalian target of rapamycin). Materials and Methods: BE-2(c) and IMR-32 neuroblastoma cell lines were treated with varying concentrations of αIR3, rapamycin and temsirolimus alone or in combination and the viable cells were counted. Results: Blockade of IGF1R signaling significantly inhibited cell growth as compared to untreated controls (p<0.05), and a combination of agents was more effective than each agent alone. Conclusion: The combination of rapamycin or temsirolimus with αIR3 blocks the IGF1R signaling pathway and has an antiproliferative effect on neuroblastoma cells warranting further investigations using inhibitors of IGF1R signaling as novel combination therapy for neuroblastoma.