Figure 1.

P-gp confers resistance to DOX-mediated caspase-dependent DNA fragmentation. (a) CEM cell lines (P-gp^low CCRF, 2H6 and 4G9, P-gp^high A7⁺, 2G10, and IC10) were labeled with ¹²⁵IUdR for 1 h, washed in growth media, and incubated for 48 h in 96-well plates (2 × 10⁴ cells/well) with DOX. (b) In some wells CCRF or A7⁺ cells also were preincubated with anti-P-gp mAb (MRK-16) or isotype control W6/32 mAb (50 μg/ml, final concentration) for 30 min, and DOX was added. Neither mAb caused more than 5% ¹²⁵IUdR release above background in the absence of DOX. (c) In some wells CCRF or A7⁺ cells were preincubated for 30 min with 20 μM (final concentration) ZVAD-fmk or control ZFA-fmk inhibitor, and DOX was added. These data are calculated as the mean ± SE of triplicate samples and are representative of at least two different experiments. DOX concentrations (μg/ml) are shown on the x-axes of each part.