ATM inhibition prevents interleukin-6 from contributing to the proliferation of glioblastoma cells after ionizing radiation
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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.
KeywordsInterleukin-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.
This article does not contain any studies with human participants or animals performed by any of the authors.
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