Antisense treatment of IGF-IR induces apoptosis and enhances chemosensitivity in central nervous system atypical teratoid/rhabdoid tumours cells

J. D'cunja, T. Shalaby, P. Rivera, A. von Büren, R. Patti, F. L. Heppner, A. Arcaro, L. B. Rorke-Adams, P. C. Phillips, M. A. Grotzer

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Central nervous system (CNS) atypical teratoid/rhabdoid tumours (AT/RT) are among the paediatric malignant tumours with the worst prognosis and fatal outcome. Insulin-like growth factor I receptor (IGF-IR) protects cancer cells from apoptosis induced by a variety of anticancer drugs and radiation. In the present study, IGF-IR was expressed in 8/8 primary AT/RT as detected by immunohistochemistry. Moreover, we found IGF-I and IGF-II mRNA in BT-16 CNS AT/RT cells and IGF-II mRNA in BT-12 CNS AT/RT cells, and autophosphorylated IGF-IR in both cell lines, indicating the potential presence of an autocrine/paracrine IGF-I/II/IGF-IR loop in CNS AT/RT. IGF-IR antisense oligonucleotide treatment of human CNS AT/RT cells resulted in significant down-regulation of IGF-IR mRNA and protein expression, induction of apoptosis, and chemosensitisation to doxorubicin and cisplatin. These studies provide evidence for the influence of IGF-IR on cellular responses to chemotherapy and raise the possibility that curability of selected CNS AT/RT may be improved by pharmaceutical strategies directed towards the IGF-IR.

Original languageEnglish
Pages (from-to)1581-1589
Number of pages9
JournalEuropean Journal of Cancer
Volume43
Issue number10
DOIs
StatePublished - Jul 2007
Externally publishedYes

Keywords

  • Antisense oligonucleotide
  • Brain tumours
  • Novel therapies
  • Rhabdoid tumour

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