Fig. 6: Disrupting AATF and XRCC4 interaction sensitizes GB to chemoradiotherapy.

a Schematic drawing of the synthesized polypeptides of AATF. NLS, nuclear localization signal. b 4121 GSCs were treated with the indicated polypeptides for 6 h. Live-cell imaging of FITC-tagged polypeptides was performed in three biologically independent experiments, and representative images are shown. Scale bars, 5 μm. c 4121 GSCs were treated with the indicated polypeptides and MG132 (10 μM) for 6 h. AATF-XRCC4 interaction was analyzed by IP with IgG or anti-AATF antibody. d 4121 GSCs preincubated with the indicated polypeptides were treated with IR (3 Gy) (top), or TMZ (50 μM) (bottom) at the indicated time points. IB analysis of γ-H2AX and XRCC4 levels are shown. The curves represent the relative levels of γ-H2AX (right, mean ± SD; Unpaired two-sided Student’s t-test). e–g BALB/c nude mice were intracranially implanted with 4121 GSCs expressing Luciferase. Mice were treated with control, IR (3 Gy, once a week, 3 times), TMZ (40 mg/kg, every two days, 5 times), the mix of three polypeptides (10 mg/kg, every two days, 5 times), or the combined treatment from day 9 post-implantation. GB xenografts were tracked by bioluminescence and the representative images are shown (e). Bioluminescent quantifications of tumor growth are shown (f, n = 6 mice for each group; mean ± SD; Unpaired two-sided Student’s t-test). Kaplan–Meier survival plots of mice are shown (g, Log-rank Mantel–Cox test). For IB, protein levels were normalized to immunoprecipitated AATF (c), or GAPDH (d). Independent experiments were performed three times with similar results (c, d). Source data are provided as a Source Data file.