Journal of Neuro-Oncology

, Volume 138, Issue 3, pp 509–518 | Cite as

ATM inhibition prevents interleukin-6 from contributing to the proliferation of glioblastoma cells after ionizing radiation

  • Yi Chieh Lim
  • Hazel Quek
  • Carolin Offenhäuser
  • Shazrul Fazry
  • Andrew Boyd
  • Martin Lavin
  • Tara Roberts
  • Bryan DayEmail author
Laboratory Investigation


Glioblastoma (GBM) is a highly fatal disease with a 5 year survival rate of less than 22%. One of the most effective treatment regimens to date is the use of radiotherapy which induces lethal DNA double-strand breaks to prevent tumour growth. However, recurrence occurs in the majority of patients and is in-part a result of robust radioresistance mechanisms. In this study, we demonstrate that the multifunctional cytokine, interleukin-6 (IL-6), confers a growth advantage in GBM cells but does not have the same effect on normal neural progenitor cells. Further analysis showed IL-6 can promote radioresistance in GBM cells when exposed to ionising radiation. Ablation of the Ataxia-telangiectasia mutated serine/threonine kinase that is recruited and activated by DNA double-strand breaks reverses the effect of radioresistance and re-sensitised GBM to DNA damage thus leading to increase cell death. Our finding suggests targeting the signaling cascade of DNA damage response is a potential therapeutic approach to circumvent IL-6 from promoting radioresistance in GBM.


Interleukin-6 Glioblastoma DNA damage response Ataxia-telangiectasia mutated Inhibitor 



This work was generously supported by the Cancer Institute New South Wales Future Research Leader fellowship.


TLR is the recipient of a Cancer Institute New South Wales Future Research Leader fellowship.

Compliance with ethical standards

Conflict of interest

All authors declare no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

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Supplementary material 4 (DOCX 23 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Yi Chieh Lim
    • 1
  • Hazel Quek
    • 1
  • Carolin Offenhäuser
    • 1
  • Shazrul Fazry
    • 2
  • Andrew Boyd
    • 1
  • Martin Lavin
    • 3
  • Tara Roberts
    • 4
    • 5
  • Bryan Day
    • 1
    Email author
  1. 1.Translational Brain Cancer Research Laboratory, Cell and Molecular Biology DepartmentQIMR Berghofer MRIBrisbaneAustralia
  2. 2.School of Bioscience and Biotechnology, Faculty of Science and TechnologyUniversiti Kebangsaan MalaysiaSelangorMalaysia
  3. 3.Faculty of MedicineThe University of Queensland Centre for Clinical ResearchHerston, BrisbaneAustralia
  4. 4.Ingham Institute for Applied Medical Research and School of MedicineWestern Sydney UniversityLiverpool, SydneyAustralia
  5. 5.South West Sydney Clinical SchoolUNSW SydneyKensington, SydneyAustralia

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