Tags

Type your tag names separated by a space and hit enter

Down-regulation of insulin-like growth factor I receptor activity by NVP-AEW541 has an antitumor effect on neuroblastoma cells in vitro and in vivo.
Clin Cancer Res. 2006 Nov 15; 12(22):6772-80.CC

Abstract

PURPOSE

Signaling through insulin-like growth factor I receptor (IGF-IR) is important for growth and survival of many tumor types. Neuroblastoma is sensitive to IGF.

EXPERIMENTAL DESIGN

We assessed the ability of NVP-AEW541, a recently developed small molecule that selectively inhibits IGF-IR activity, for neuroblastoma growth effects in vitro and in vivo. Our data showed that, in a panel of 10 neuroblastoma cell lines positive for IGF-IR expression, NVP-AEW541 inhibited in vitro proliferation in a submicromolar/micromolar (0.4-6.8) range of concentrations.

RESULTS

As expected, NVP-AEW541 inhibited IGF-II-mediated stimulation of IGF-IR and Akt. In addition to growth inhibition, the drug also induced apoptosis in vitro. Oral administration of NVP-AEW541 (50 mg/kg twice daily) inhibited tumor growth of neuroblastoma xenografts in nude mice. Analysis of tumors from the drug-treated animals revealed a marked apoptotic pattern and a decrease in microvascularization compared with controls. Interestingly, quantitative real-time PCR detected both in vitro and in vivo a significant down-regulation of mRNA for vascular endothelial growth factor (VEGF) caused by NVP-AEW541. In addition, in Matrigel-coated chambers and in severe combined immunodeficient mice tail vein injected with neuroblastoma cells, tumor invasiveness was significantly reduced by this agent. Analysis of IGF-IR expression in a series of 43 neuroblastoma primary tumors revealed IGF-IR positivity in 86% of cases.

CONCLUSIONS

Taken together, these data indicate that NVP-AEW541 can be considered as a novel promising candidate for treatment of neuroblastoma patients.

Authors+Show Affiliations

Section of Toxicology and Biomedical Sciences, Ente per le Nuove tecnologie l'Energia e l'Ambiente, Research Center Casaccia, La Sapienza University, Department of Pediatrics, Laboratory of Oncology, Bambino Gesù Children's Hospital, Rome, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17121898

Citation

Tanno, Barbara, et al. "Down-regulation of Insulin-like Growth Factor I Receptor Activity By NVP-AEW541 Has an Antitumor Effect On Neuroblastoma Cells in Vitro and in Vivo." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 12, no. 22, 2006, pp. 6772-80.
Tanno B, Mancini C, Vitali R, et al. Down-regulation of insulin-like growth factor I receptor activity by NVP-AEW541 has an antitumor effect on neuroblastoma cells in vitro and in vivo. Clin Cancer Res. 2006;12(22):6772-80.
Tanno, B., Mancini, C., Vitali, R., Mancuso, M., McDowell, H. P., Dominici, C., & Raschellà, G. (2006). Down-regulation of insulin-like growth factor I receptor activity by NVP-AEW541 has an antitumor effect on neuroblastoma cells in vitro and in vivo. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 12(22), 6772-80.
Tanno B, et al. Down-regulation of Insulin-like Growth Factor I Receptor Activity By NVP-AEW541 Has an Antitumor Effect On Neuroblastoma Cells in Vitro and in Vivo. Clin Cancer Res. 2006 Nov 15;12(22):6772-80. PubMed PMID: 17121898.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Down-regulation of insulin-like growth factor I receptor activity by NVP-AEW541 has an antitumor effect on neuroblastoma cells in vitro and in vivo. AU - Tanno,Barbara, AU - Mancini,Camillo, AU - Vitali,Roberta, AU - Mancuso,Mariateresa, AU - McDowell,Heather P, AU - Dominici,Carlo, AU - Raschellà,Giuseppe, PY - 2006/11/24/pubmed PY - 2007/2/7/medline PY - 2006/11/24/entrez SP - 6772 EP - 80 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 12 IS - 22 N2 - PURPOSE: Signaling through insulin-like growth factor I receptor (IGF-IR) is important for growth and survival of many tumor types. Neuroblastoma is sensitive to IGF. EXPERIMENTAL DESIGN: We assessed the ability of NVP-AEW541, a recently developed small molecule that selectively inhibits IGF-IR activity, for neuroblastoma growth effects in vitro and in vivo. Our data showed that, in a panel of 10 neuroblastoma cell lines positive for IGF-IR expression, NVP-AEW541 inhibited in vitro proliferation in a submicromolar/micromolar (0.4-6.8) range of concentrations. RESULTS: As expected, NVP-AEW541 inhibited IGF-II-mediated stimulation of IGF-IR and Akt. In addition to growth inhibition, the drug also induced apoptosis in vitro. Oral administration of NVP-AEW541 (50 mg/kg twice daily) inhibited tumor growth of neuroblastoma xenografts in nude mice. Analysis of tumors from the drug-treated animals revealed a marked apoptotic pattern and a decrease in microvascularization compared with controls. Interestingly, quantitative real-time PCR detected both in vitro and in vivo a significant down-regulation of mRNA for vascular endothelial growth factor (VEGF) caused by NVP-AEW541. In addition, in Matrigel-coated chambers and in severe combined immunodeficient mice tail vein injected with neuroblastoma cells, tumor invasiveness was significantly reduced by this agent. Analysis of IGF-IR expression in a series of 43 neuroblastoma primary tumors revealed IGF-IR positivity in 86% of cases. CONCLUSIONS: Taken together, these data indicate that NVP-AEW541 can be considered as a novel promising candidate for treatment of neuroblastoma patients. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/17121898/Down_regulation_of_insulin_like_growth_factor_I_receptor_activity_by_NVP_AEW541_has_an_antitumor_effect_on_neuroblastoma_cells_in_vitro_and_in_vivo_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=17121898 DB - PRIME DP - Unbound Medicine ER -