Fig. 3.

Aspirin and APT102 in combination significantly decreased metastatic tumor burden in a second murine tumor model. BALB/c mice were treated with either vehicle or ASA + ATP102 30-min prior to i.c. inoculation of 4T1-GFP-FL cells, and drug treatments continued for 2½ days. BLI was performed at days 2 and 9 after tumor inoculation and skeletal tumor burden was measured in a consistent region of interest (ROI). A: 4T1-GFP-FL metastatic tumor burden is significantly decreased in the femur/tibia (day 2, P=0.01; day 9, P=0.02) of mice treated with ASA+APT102 (n=15) compared to control (n = 15). B: Representative images of BLI at day 2.C: Representative histological sections of tibia. T = Tumor, M ¼ Marrow. D: Tumor volume was measured by histomorphometric analysis on paraffin-embedded femurs of mice sacrificed 9 days after tumor inoculation. Tumor volume was decreased in femurs of mice treated with ASA+APT102 compared to vehicle (P = 0.04). (ASA + APT102 treated bones n = 30, vehicle treated bones n = 30.) E: Representative radiographic images of femur/ tibia taken at day 14. Arrows show areas of tumor-associated osteolysis. F: Serial weights were performed on mice starting at day 0 prior to tumor inoculation for 11 days. Average weight loss is plotted in grams. Vehicle treated mice lost significantly moreweightaftertumorinoculationcomparedtoASA+APT102 treated mice (vehicle n = 8, ASA+APT102 n = 5, D0-D11 P = 0.04).