IGF-I receptor inhibition combined with rapamycin or temsirolimus inhibits neuroblastoma cell growth.
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, alphaIR3. Inhibition of IGF1R signaling can be accomplished by other agents, including rapamycin or temsirolimus, which target mTOR (mammalian target of rapamycin).


METHODS
BE-2(c) and IMR-32 neuroblastoma cell lines were treated with varying concentrations of alphaIR3, 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.


CONCLUSIONS
The combination of rapamycin or temsirolimus with alphaIR3 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.
Coulter
Don W
DW
Division of Hematology-Oncology, Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7220, USA. dcoulter@unch.unc.edu
Blatt
Julie
J
D'Ercole
A Joseph
AJ
Moats-Staats
Billie M
BM
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011494:Protein Kinases / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases
C401859:temsirolimus; D011494:Protein Kinases; C546842:MTOR protein, human; D017526:Receptor, IGF Type 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus