Figure 4:

Auranofin sensitized tumor and protected intestine from abdominal radiotherapy. A) Schematic diagram of auranofin treatment (10 mg/kg i.p.) and fractionated AIR (4 Gy/fraction) given to BALB/c mice with a CT26 colon tumor implanted in the abdominal flank. B) Mice receiving auranofin prior to AIR exposure demonstrated significant tumor growth retardation compared to DMSO control (p<0.0005), AIR (p<0.003), or auranofin only (p<0.005) treatment (n=10 mice/group). C) Representative picture of CT26 colon tumor at day 25 after first auranofin treatment. D) Immunoblot to detect p53 and p21 protein expression in CT26 colon tumor cells. No significant difference in p53 and p21 protein expression level was observed in auranofin and AIR treatment groups compared to DMSO control. Representative immunoblot images from at least three independent experiments with β-actin loading control. E) Schematic diagram of the treatment protocol and the AIR (12.5 Gy) exposure field for BALB/c mice. A 3 cm square area of the mice containing the GI tract was irradiated (irradiation field), thus shielding the upper thorax, head and neck as well as the lower and upper extremities, protecting a significant portion of the bone marrow. Mice were treated with auranofin (10 mg/kg i.p.) prior to single dose AIR (12.5 Gy). F) Kaplan–Meier survival analysis indicated a significant improvement in survival for the AUR+AIR groupcompared to AIR alone (p<0.0001; log rank (Mantel–Cox) test; n=10 mice per group). G) Body weight of mice at times post AIR. H) Combination treatment of auranofin and single dose AIR resulted in significant reductionof tumor growth compared to the auranofin only (p<0.002) and DMSO control (p<0.001).