Table 1.
Biological activity of sorafenib in acute myeloid leukemia cell lines*
| Cell line | Mean IC50† (95% CI), μM | Mean proliferation‡, % |
Apoptosis§ (95% CI), % |
Mean levels of phospho-ERK‖ (95% CI), AU |
Mean levels of phospho-p70S6K‖ (95% CI), AU |
Mean levels of phospho-AKT‖ (95% CI), AU |
|||||
| Concentration of sorafenib, μM | |||||||||||
| 0 | 10 | 0 | 10 | 0 | 10 | 0 | 10 | 0 | 10 | ||
| HL-60 | 3.3 (2.2 to 4.4) | 61 | 6.2 | 12 (0 to 25) | 89 (77 to 101) | 982 (463 to 1502) | 159 (102 to 217) | 5698 (4263 to 7132) | 3024 (1149 to 4899) | 121 (62 to 179) | 95 (40 to 150) |
| Kasumi-1 | 0.04 (0.01 to 0.07) | 30 | 2.5 | 31 (9 to 53) | 87 (72 to 101) | 162 (117 to 208) | 133 (105 to 162) | 1441 (1226 to 1655) | 286 (245 to 328) | 99 (65 to 134) | 66 (46 to 86) |
| KG-1 | 2.6 (0.33 to 5.0) | 48 | 5.3 | 28 (13 to 43) | 45 (23 to 67) | 243 (179 to 308) | 139 (115 to 164) | 5370 (3191 to 7550) | 1954 (1013 to 2898) | 84 (66 to 102) | 84 (73 to 95) |
| ML-2 | 3.7 (2.0 to 5.4) | 131 | 4.5 | 9.4 (0 to 19) | 94 (92 to 97) | 116 (0 to 239) | 55 (20 to 90) | 61 (42 to 80) | 64 (36 to 91) | 53 (34 to 72) | 38 (27 to 50) |
| U937 | 6.9 (5.6 to 8.2) | 63 | 51 | 6.0 (1 to 11) | 56 (33 to 79) | 1192 (691 to 1693) | 155 (121 to 189) | 1183 (866 to 1500) | 752 (535 to 969) | 1451 (710 to 2192) | 148 (120 to 176) |
| MV4-11 | 0.002 (0.0002 to 0.004) | 28 | 0.5 | 15 (0 to 38) | 90 (69 to 111) | 1194 (650 to 1739) | 103 (82 to 124) | 5123 (2641 to 7604) | 779 (362 to 1196) | 230 (216 to 244) | 147 (88 to 206) |
| Mo7e | 9.1 (8.4 to 9.8) | 47 | 1.6 | 22 (17 to 27) | 42 (37 to 47) | 154 (121 to 187) | 143 (113 to 172) | 3179 (2535 to 3824) | 1252 (632 to 1872) | 114 (28 to 200) | 135 (41 to 229) |
| THP-1 | 6.2 (2.9 to 9.6) | 50 | 2.1 | 12 (0 to 34) | 36 (14 to 58) | 415 (271 to 559) | 86 (53 to 120) | 937 (0 to 2343) | 162 (13 to 310) | 180 (67 to 293) | 106 (48 to 164) |
| NB4 | 7.3 (3.0 to 11.5) | 74 | 10 | 27 (23 to 31) | 55 (37 to 74) | 1081 (978 to 1185) | 260 (187 to 332) | 6753 (4484 to 9023) | 3465 (2159 to 4770) | 179 (102 to 257) | 104 (58 to 151) |
| OCI-AML3 | 3.9 (3.3 to 4.4) | 140 | 4.2 | 13 (8 to 19) | 82 (33 to 81) | 1706 (910 to 2502) | 227 (48 to 405) | 281 (185 to 378) | 84 (61 to 107) | 199 (72 to 327) | 95 (61 to 129) |
The data are the mean with 95% confidence interval (CI) calculated using the t distribution at a confidence level of P = .05. When only two replicate measurements were obtained, the 95% confidence interval was not reported. AU = arbitrary units of fluorescence.
IC50 = the concentration (μM) inhibiting cell viability by 50% compared with dimethyl sulfoxide-treated control cells. Data represent the average of three independent experiments.
Proliferation was measured by use of a 5-ethynyl-2′-deoxyuridine cell proliferation kit and flow cytometer. The mean number of Alexa Fluor 488 positive–staining cells from treated vs untreated cells are shown. Values were calculated by comparing the treated cells to untreated cells. Data are from two or three independent experiments with one replicate each.
Apoptosis was measured by use of an Annexin V-FITC/7-AAD kit and flow cytometer. The mean number of Annexin V–positive staining cells from treated vs untreated control cells are shown. Data are from three independent experiments with one replicate each.
Mean levels of phosphoproteins were measured by a quantitative bead-based multiplex phosphoprotein assay. Data are from two independent experiments with two replicates each.