Figure 3.
Effect of multidrug resistance reversal agents on GO-induced cytotoxicity in Pgp-positive/MRP-positive AML blast cell samples. The 17 patient samples are ordered (1-17) from the lowest to the highest DiOC2 inhibitor-modulating factor values for CSA (range, 1.02-3.15). The effect of GO alone or GO in combination with the MRP inhibitor MK-571, the Pgp inhibitor CSA, or MK-571+CSA are depicted as the percentage increases in apoptosis (A) or necrosis (B) compared with patient samples treated with the control immunoconjugate CTM01. GO-induced cytotoxicity (apoptosis, necrosis, or both) was significantly enhanced by MK-571 alone in sample 1, whereas MK-571 further enhanced the effect of CSA on GO-induced cytotoxicity in samples 2, 5, and 16 (*P < .05). These effects were confirmed in a second independent experiment. CSA alone caused significant enhancement (P < .05) in GO-induced cytotoxicity in samples 1, 2, 5-8, 11-13, and 15-17. Values are shown as mean ± SD of triplicate assays.