Figure 5. Pemetrexed and sorafenib interact to suppress breast cancer tumor growth in orthotopic human and rodent syngeneic model systems.

Panel A. BT474 tumors were established in the 4^th mammary fat pad of athymic mice (~75 mm³). Animals were treated with vehicle, sorafenib (sor), pemetrexed (ptx) or both drugs simultaneously as described in Methods. Animals were treated for 5 days with drugs and tumor volumes measured every two-three days as indicated, and mean tumor volumes plotted (n = 2 studies; 8 animals per group total +/− SEM; * p < 0.05 less than corresponding vehicle control value; % p < 0.05 less than corresponding sorafenib value). Panel B. BT474 tumors fourteen days after drug exposure were fixed, sectioned and stained as described in Methods. Ki67 measures tumor cell proliferative rate; TUNEL and cleaved caspase 3 the levels of tumor cell apoptosis within the tumors. Panel C. 4T1 tumors were injected into the 4^th mammary fat pad of BALB/c mice. Five days after implantation the animals were administered vehicle, sorafenib (sor), pemetrexed (ptx) or both drugs simultaneously as described in Methods for 5 days. The volumes of the tumors in each group were calculated 14 days after the final drug treatment (n = 2 studies; 8 animals per group total +/− SEM; * p < 0.05 less than ptx or sor treated tumor values).