Fig. 7
Inhibiting DNA-PK enhances oncolytic therapy in murine cancer models and patient tumour samples. a Timeline of the experimental setup for b, c. b, c HCT-116 xenografts were treated with vehicle, M1 virus (2 × 106 pfu, i.v., intravenously injection), NU7441 (10 mg/kg/day, i.p., intraperitoneal.) or a combination. Vehicle, n = 6; M1, n = 6; NU7441, n = 7; NU7441 + M1, n = 7. b Tumour growth presented as the mean tumour volume ± SD. **P < 0.01 for NU7441 + M1 group versus single agents. Statistical significance was using repeated measure ANOVA. c Representative images of tumours from each group in b at the experimental endpoints. d Timeline of the experimental setup for e, f. e, f BxPC-3 xenografts were treated with vehicle, M1 virus (2 × 106 pfu, i.v., intravenously injection), NU7441 (10 mg/kg/day, i.p., intraperitoneal.) or a combination. Vehicle, n = 5; M1, n = 5; NU7441, n = 5; NU7441 + M1, n = 7. e Tumour growth is presented as the mean tumour volume ± SD. **P < 0.01 for NU7441 + M1 group versus single agents. Statistical significance was using repeated measure ANOVA. f Representative images of tumours from each group in e at the experimental endpoints. g Tumour tissues from c were evaluated through immunohistochemistry for p-H2AX (a marker of DSBs), Ki-67 (a marker of proliferation) and cleaved-caspase-3 (a marker of cell apoptosis). Scale bar: 50 μm. h Tumour tissues from f were evaluated through immunohistochemistry for p-H2AX, Ki-67 and cleaved-caspase-3. Scale bar: 50 μm. i Tumour infiltrating T cells from immunocompetent C57/BL6 mice were evaluated through immunohistochemistry for CD4 and CD8. Scale bar: 50 μm. j Primary colorectal tumour cells isolated from six patients were treated with vehicle, NU7441 (1 μM), M1 (MOI = 1) or a combination for 72 h, and cell viability was assessed. P represent Patient
