Tumor relapse after radiotherapy is a great concern in the treatment of 
high-grade gliomas. Inhibition of the PI3-kinase/AKT pathway is known to 
radiosensitize cancer cells and to delay their DNA repair after irradiation. In 
this study, we show that the radiosensitization of CB193 and T98G, two 
high-grade glioma cell lines, by the PI3K inhibitor LY294002, correlates with 
the induction of G1 and G2/M arrest, but is inconsistently linked to a delayed 
DNA double-strand break (DSBs) repair. The PI3K/AKT pathway has been shown to 
activate radioprotective factors such as telomerase, whose inhibition may 
contribute to the radiosensitization of cancer cells. However, we show that 
radiation upregulates telomerase activity in LY-294002-treated glioma cells as 
well as untreated controls, demonstrating a PI3K/AKT-independent pathway of 
telomerase activation. Our study suggests that radiosensitizing strategies based 
on PI3-kinase inhibition in high-grade gliomas may be optimized by additional 
treatments targeting either telomerase activity or telomere maintenance.