Figure 5
Figure 5. Treatment with AMD3100, FC-131, or a CXCR4 blocking antibody significantly increases PS-mediated lethality of AML cells. (A) Analysis of the dose-effect relationship for PS (5-50nM) and AMD3100 (2-10μM) or FC-131 (0.5-4μM) for the apoptotic effects after 48 hours of exposure in OCI-AML3 cells was performed according to the median dose effect method of Chou and Talalay. After this, the CI values were calculated using the percentage of apoptotic cells (fraction affected [FA]) by the 2 agents together. CI < 1, CI = 1, and CI > 1 represent synergism, additivity, and antagonism of the 2 agents, respectively. (B) Primary AML (n = 8) and CD34+ peripheral blood mononuclear cells from healthy donors were treated with the indicated concentrations of FC-131 and/or PS for 48 hours. Then, the percentages of nonviable cells were determined by trypan blue dye uptake in a hemocytometer. (C) OCI-AML3 cells were treated with the indicated concentrations of anti-CXCR4 MAB-172 antibody and/or PS for 48 hours. Then, the percentages of apoptotic cells were determined by annexin V and propidium iodide staining and flow cytometry. Columns represent the mean of 3 experiments. Bars represent the SEM.

Treatment with AMD3100, FC-131, or a CXCR4 blocking antibody significantly increases PS-mediated lethality of AML cells. (A) Analysis of the dose-effect relationship for PS (5-50nM) and AMD3100 (2-10μM) or FC-131 (0.5-4μM) for the apoptotic effects after 48 hours of exposure in OCI-AML3 cells was performed according to the median dose effect method of Chou and Talalay. After this, the CI values were calculated using the percentage of apoptotic cells (fraction affected [FA]) by the 2 agents together. CI < 1, CI = 1, and CI > 1 represent synergism, additivity, and antagonism of the 2 agents, respectively. (B) Primary AML (n = 8) and CD34+ peripheral blood mononuclear cells from healthy donors were treated with the indicated concentrations of FC-131 and/or PS for 48 hours. Then, the percentages of nonviable cells were determined by trypan blue dye uptake in a hemocytometer. (C) OCI-AML3 cells were treated with the indicated concentrations of anti-CXCR4 MAB-172 antibody and/or PS for 48 hours. Then, the percentages of apoptotic cells were determined by annexin V and propidium iodide staining and flow cytometry. Columns represent the mean of 3 experiments. Bars represent the SEM.

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