Vasoactive intestinal peptide decreases MYCN expression and synergizes with retinoic acid in a human MYCN-amplified neuroblastoma cell line

  • Authors:
    • Lucie Chevrier
    • Annie-Claire Meunier
    • Stéphanie Cochaud
    • Jean-Marc Muller
    • Corinne Chadéneau
  • View Affiliations

  • Published online on: November 1, 2008     https://doi.org/10.3892/ijo_00000097
  • Pages: 1081-1089
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Abstract

Neuroblastoma is a pediatric tumor which can spontaneously regress or differentiate into a benign tumor. MYCN oncogene amplification occurs in 22% of neuroblastomas and is associated with poor prognosis. Retinoic acid (RA), a molecule able to induce differentiation and to decrease MYCN expression, is used in the therapy of neuroblastomas. The neuropeptide vasoactive intestinal peptide (VIP) is known to control proliferation or differentiation of numerous cancer cells. In vitro, VIP induces differentiation of neuroblastoma cells. To determine whether VIP could modulate MYCN expression, we carried out real-time quantitative RT-PCR and Western immunoblot analyses in human neuroblastoma SH-SY5Y and IMR-32 cells. The results indicated that VIP reduced MYCN mRNA and protein expression, especially in the MYCN-amplified IMR-32 cells, with a maximal and transient decrease by ≈50% after few hours of treatment with VIP at 10−6 M. This effect was compared to that of RA at 10−5 M, which induced a diminution of MYCN mRNA expression by ≈25% after few days of treatment. This indicated that VIP and RA display complementary kinetics. Cotreatments showed that VIP and RA had synergistic effects on regulation of expression of MYCN proteins. VIP and RA cotreatments regulated also expression of two MYCN target genes, SKP2 and TP53INP1. These results suggest that VIP, in combination with RA may have a potential therapeutic benefit in neuroblastomas with MYCN amplification, a genetic abnormality associated with poor prognosis.

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November 2008
Volume 33 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Chevrier L, Meunier A, Cochaud S, Muller J and Chadéneau C: Vasoactive intestinal peptide decreases MYCN expression and synergizes with retinoic acid in a human MYCN-amplified neuroblastoma cell line. Int J Oncol 33: 1081-1089, 2008.
APA
Chevrier, L., Meunier, A., Cochaud, S., Muller, J., & Chadéneau, C. (2008). Vasoactive intestinal peptide decreases MYCN expression and synergizes with retinoic acid in a human MYCN-amplified neuroblastoma cell line. International Journal of Oncology, 33, 1081-1089. https://doi.org/10.3892/ijo_00000097
MLA
Chevrier, L., Meunier, A., Cochaud, S., Muller, J., Chadéneau, C."Vasoactive intestinal peptide decreases MYCN expression and synergizes with retinoic acid in a human MYCN-amplified neuroblastoma cell line". International Journal of Oncology 33.5 (2008): 1081-1089.
Chicago
Chevrier, L., Meunier, A., Cochaud, S., Muller, J., Chadéneau, C."Vasoactive intestinal peptide decreases MYCN expression and synergizes with retinoic acid in a human MYCN-amplified neuroblastoma cell line". International Journal of Oncology 33, no. 5 (2008): 1081-1089. https://doi.org/10.3892/ijo_00000097