Total cellular doxorubicin uptake was measured in multiple cell lines (AdRr, OVCAR8, MCF7, HeLa, MKN-45, IGROV1, ZR75-1, MDA-MB-361, MDA-MB-453, 4T1-clone-12W7, OVCAR8-Her2, HCC1954, AdRr-Her2, JIMT-1, MCF7-c18, Calu-3, MKN-7, NCI-N87, SkBr3, SKOV3, and BT474-M3) following incubation with 3, 15, or 75 µg/ml of doxorubicin (squares, circles, and triangles, respectively) for up to 3 hours. (a) Time courses for 21 different cell lines following incubation with 15 µg/ml doxorubicin. The kinetic model for doxorubicin transport into and out of cells (see Figure 1b) was fit to the experimental data for each to estimate rates of doxorubicin-cell association (kf_ol) and rate of outward flippase/efflux activity (kflippase_out). (b) A representative model fit (solid lines) to data for the OVCAR8-Her2 cell line for 3, 15, and 75 µg/ml data (circles, squares, triangles, respectively). (c,d) Histograms of the fitted parameter values for kf_ol and kflippase_out, respectively.