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

作者：Lim Yi Chieh; Quek Hazel; Offenhauser Carolin; Fazry Shazrul; Boyd Andrew; Lavin Martin; Roberts Tara; Day Bryan^*

来源：Journal of Neuro-Oncology, 2018, 138(3): 509-518.

DOI：10.1007/s11060-018-2838-0

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

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.

• 出版日期2018-7