Fig. 5

MCL-1 antagonism increased the sensitivity of MDA-MB-231-2A cells to dasatinib. (a) Representative immunohistochemistry images using antibodies against multi-Cytokeratin on contracted matrices seeded with MDA-MB-231-2A cells treated with vehicle, DOX, dasatinib or their combination at day 1 invasion and collected 10 days post invasion. Bar graphs depicting the average invasive index (b; total number of cells within the matrix expressed as a proportion of the number of cells on top with the opportunity to invade), the average proliferative index (c; ratio of Ki67-positive cells to total number of cells) and the average apoptotic index (d; ratio of CC3-positive cells to total number of cells). Average of three independent experiments. Bars indicate significantly significant groups, p value unpaired t tests. (e) Schematic representation of BIMs2A and dasatinib combination experiment using MDA-MB-231-2A in vivo mammary intraductal xenografts. (f) Representative Carmine-stained mammary whole mounts of MDA-MB-231-2A mammary intraductal xenografts 9 weeks after inoculation from mice treated with vehicle (n = 13), DOX (n = 10), dasatinib (n = 10) and a combination of both (n = 10). (g) Bar graphs depicting the total number of tumors (resectable and present in the mammary whole mount) or palpable from mice with MDA-MB-231-2A mammary intraductal xenografts 9 weeks after inoculation. Chi-squared p value and numbers of mice indicated within the bars. (h) Number of metastases from mice treated with vehicle, DOX, dasatinib and a combination of both. Bars indicate statistically significant groups, Mann–Whitney p value. DOX doxycycline