Fig. 3.

a Representative bioluminescent images of mice bearing TKCC05 pancreatic cancer xenografts at surgery (baseline) or at 5 weeks after surgery (5 weeks) and treated with vehicle (n = 7), 25 mg/kg S63845 (n = 7), 10 mg/kg dasatinib (n = 5, 2 were excluded from the dasatinib cohort as they reached ethical end point one week early due to ascites) or combined S63845 and dasatinib (n = 7). b Line graphs of the average bioluminescence of mice bearing TKCC05 pancreatic cancer xenografts at surgery (baseline) over a 5 week period treated with vehicle, 25 mg/kg S63845, 10 mg/kg dasatinib or combined S63845 and dasatinib. Dot plots of c tumor weight, d tumor Ki67 positivity (e) and cleaved caspase 3 positivity in TKCC05 pancreatic cancer orthotopic primary tumors. Representative photomicrographs taken at ×20 objective of the f lungs and g livers from mice bearing TKCC05 pancreatic cancer xenografts subjected to immunohistochemistry using an antibody against vimentin and (h) dot plots showing the average area of metastasis in the lungs and (i) livers of mice bearing TKCC05 pancreatic cancer xenografts at 5 weeks post surgery (each dot is average of 15 images within one mouse). Unpaired t-tests between groups and one-way ANOVA p-value for treatments (vehicle vs. S63845) illustrated. j Model schematic of MCL-1 and SRC regulation of Cofilin. Combined inhibition of MCL-1 by BH3 mimetics such as S63845 and A1210477 can enhance the anti-invasive effects of dasatinib via a possible direct or indirect regulation of Cofilin via SRC