Table 3.
Selonsertib sensitized ABCG2-substrate-selected resistant cell lines to ABCG2 substrates.
| Treatment | IC50 ± SDa (RFb) |
|||
|---|---|---|---|---|
| NCI-H460 (μM) | NCI-H460/MX20 (μM) | S1 (μM) | S1-M1–80 (μΜ) | |
| Mitoxantrone | 0.038 ± 0.003 (1.00) | 5.139 ± 0.801 (135.01) | 0.033 ± 0.007 (1.00) | 2.700 ± 0.711 (81.52) |
| +Selonsertib (3 μM) | 0.031 ± 0.001 (0.82) | 0.557 ± 0.036 (14.63)* | 0.033 ± 0.014 (0.99) | 0.540 ± 0.521 (16.30)* |
| +Selonsertib (10 μM) | 0.027 ± 0.002 (0.71) | 0.385 ± 0.061 (10.12)* | 0.034 ± 0.009 (1.03) | 0.133 ± 0.082 (4.01)* |
| +Ko 143 (10 μM) | 0.030 ± 0.001 (0.80) | 0.428 ± 0.091 (11.24)* | 0.036 ± 0.015 (1.08) | 0.064 ± 0.018 (1.92)* |
| SN-38 | 0.039 ± 0.009 (1.00) | 3.493 ± 0.129 (88.80) | 0.047 ± 0.006 (1.00) | 2.336 ± 0.345 (50.04) |
| +Selonsertib (3 μM) | 0.021 ± 0.002 (0.53) | 0.463 ± 0.424 (11.77)* | 0.061 ± 0.005 (1.31) | 1.346 ± 0.674 (28.83)* |
| +Selonsertib (10 μM) | 0.023 ± 0.006 (0.58) | 0.178 ± 0.080 (4.51)* | 0.056 ± 0.013 (1.21) | 0.421 ± 0.359 (9.02)* |
| +Ko 143 (10 μM) | 0.018 ± 0.004 (0.46) | 0.104 ± 0.065 (2.65)* | 0.035 ± 0.014 (0.75) | 0.076 ± 0.014 (1.63)* |
| Topotecan | 0.066 ± 0.003 (1.00) | 4.113 ± 0.738 (62.72) | 0.065 ± 0.002 (1.00) | 2.492 ± 0.210 (38.54) |
| +Selonsertib (3 μM) | 0.049 ± 0.001 (0.75) | 0.909 ± 0.453 (13.86)* | 0.061 ± 0.004 (0.94) | 1.167 ± 0.733 (18.05)* |
| +Selonsertib (10 μM) | 0.046 ± 0.002 (0.70) | 0.311 ± 0.150 (4.74)* | 0.077 ± 0.023 (1.19) | 0.168 ± 0.184 (2.60)* |
| +Ko 143 (10 μM) | 0.047 ± 0.002 (0.71) | 0.212 ± 0.129 (3.23)* | 0.069 ± 0.004 (1.07) | 0.197 ± 0.075 (3.05)* |
| Cisplatin | 2.061 ± 0.500 (1.00) | 2.889 ± 0.861 (1.40) | 1.770 ± 0.285 (1.00) | 1.918 ± 0.462 (1.08) |
| +Selonsertib (3 μM) | 1.580 ± 0.281 (0.77) | 2.928 ± 1.224 (1.42) | 2.016 ± 0.262 (1.14) | 2.169 ± 0.304 (1.23) |
| +Selonsertib (10 μM) | 1.621 ± 0.165 (0.79) | 2.813 ± 0.695 (1.37) | 2.268 ± 0.212 (1.28) | 2.325 ± 0.283 (1.31) |
| +Ko 143 (10 μM) | 2.554 ± 1.115 (1.24) | 2.717 ± 1.453 (1.32) | 1.952 ± 0.191 (1.10) | 2.286 ± 0.255 (1.29) |
indicates p < 0.05 versus group treated with anticancer drug only.
IC50 values were determined by MTT assay as described in “materials and methods”, and were obtained from three independent experiments in triplicate.
Resistance fold (RF) was calculated from dividing the IC50 values of parental cells or resistance cells by the IC50 of parental cells in the of selonsertib or positive control inhibitor.