(A) Representative images of H&E staining showing the effects of chronic p38 MAPK inhibition on cancer treated bones. Panels a and b demonstrate that breast cancer cells filled the intramedullary space of the femur within 13 days following injection. In addition, areas of new bone growth were evident within the intramedullary space in the breast cancer-treated mice treated with vehicle. The cortical bone displayed an uneven look showing tumor invasion into the bone. Panels c - f show that systemic delivery of the p38 MAPK inhibitor (15 and 30 mg/kg, i.p., 2× daily) across 7 days diminished tumor burden, blocked the new bone growth within the intramedullary space and reduced the invasion of breast cancer cells into the cortical bone. B, cortical bone; M, bone marrow; T, tumor; EP, epiphyseal plate; WB, woven bone. (B) Quantification of tumor bearing area show two fold reduction in mice treated with 15 mg/kg and five-fold reduction in mice treated with 30 mg/kg of SB203580 as compared to vehicle treated mice (n = 4-5). Graph shows mean ± SEM. *indicates significant difference from vehicle-treated bones (p < 0.05) (C) Sulforhodamine B (SRB) assay shows dose dependent reduction in cell viability on treatment of breast cancer cells with SB203580 for 48 h as compared to the breast cancer cells treated with vehicle alone (n = 3). Graph shows means ± SEM. *Indicates significant difference from DMSO-treated (control) group (p < 0.05).