Hsp32/HO-1-targeting drugs inhibit growth of imatinib-resistant CML cells. (A) Imatinib-resistant K562 cells were incubated in medium containing various concentrations of ZnDPPIX (left), PEG-ZnPP (middle), or SMA-ZnPP (right) for 48 hours. Growth-inhibitory effects were quantified by ³H-thymidine incorporation assay. Results show the percentage of ³H-thymidine uptake compared with medium control (100%) and represent the mean (± SD) of 3 independent experiments. *P < .05 compared with medium control. (B) Ba/F3 cells expressing wt BCR/ABL or various imatinib-resistant mutants of BCR/ABL were incubated with various concentrations of SMA-ZnPP for 48 hours. Thereafter, proliferation was measured by ³H-thymidine incorporation. Results are expressed as percent of control and represent the mean (± SD) of triplicates from one representative experiment. (C) Isolated leukemic cells from 3 patients with imatinib-resistant CML were treated with PEG-ZnPP for 48 hours. Thereafter, proliferation was measured by ³H-thymidine incorporation assay. Results are expressed as percent of control and represent the mean (± SD) of 3 independent experiments (3 patients). *P < .05 compared with control. (D) Isolated leukemic cells from a patient with imatinib-resistant CML carrying BCR/ABL T315I, were treated with PEG-ZnPP (left panel) or SMA-ZnPP (right panel) for 48 hours. Thereafter, ³H-thymidine incorporation was measured. Results show the percentage of ³H-thymidine uptake compared with control (100%) and represent the mean (± SD) of triplicates. (E) Ba/F3p210^wt (left panel) and Ba/F3p210^T315I cells (right panel) were injected subcutaneously into nude mice (4 in each group). 7 days after tumor inoculation, when visible tumors had developed, mice were treated with PEG-ZnPP (3 mM, 0.1 mL, equivalent to 5 mg of ZnPP/kg) intravenously 3 times a week over a period of 2 weeks. Mice in the control group received physiological saline instead of PEG-ZnPP. On day 30, mice were killed, and tumor nodules were excised and weighed.