Table 1.
The cytotoxicity of tivantinib in cells overexpressing ABCG2.
| Cell Line | IC50 ± SD a μM, (Resistance-fold b) | |||
|---|---|---|---|---|
| Mitoxantrone | Mitoxantrone + Ko143 5 μM |
Tivantinib | Tivantinib + Ko143 5 μM |
|
| NCI-H460 | 0.025 ± 0.016 (1.00) | 0.022 ± 0.007 (0.89) | 0.764 ± 0.291 (1.00) | 0.640 ± 0.394 (0.84) |
| NCI-H460/MX20 | 1.939 ± 0.759 * (78.56) | 0.055 ± 0.014 (2.22) | 3.295 ± 0.375 * (4.32) | 0.914 ± 0.247 (1.20) |
| S1 | 0.033 ± 0.015 (1.00) | 0.026 ± 0.011 (0.79) | 0.712 ± 0.038 (1.00) | 0.643 ± 0.136 (0.90) |
| S1-M1-80 | 4.563 ± 1.513 * (140.04) | 0.138 ± 0.044 (4.22) | 2.391 ± 0.442 * (3.36) | 0.756 ± 0.193 (1.06) |
| HEK293/pcDNA3.1 | 0.024 ± 0.010 (1.00) | 0.026 ± 0.011 (1.07) | 3.333 ± 1.702 (1.00) | 4.404 ± 1.549 (1.32) |
| HEK293/ABCG2-WT | 0.521 ± 0.123 * (21.29) | 0.042 ± 0.009 (1.70) | 18.151 ± 3.860 * (5.45) | 7.347 ± 2.755 * (2.20) |
| HEK293/ABCG2-R482G | 1.099 ± 0.301 * (44.87) | 0.119 ± 0.023 (4.85) | 17.216 ± 7.144 * (5.16) | 4.640 ± 1.587 (1.39) |
| HEK293/ABCG2-R482T | 1.082 ± 0.174 * (44.20) | 0.033 ± 0.017 (1.35) | 10.752 ± 2.168 * (3.23) | 4.328 ± 1.661 (1.30) |
a The half maximal inhibitory concentration (IC50) values are represented as mean ± SD of at least three independent experiments performed in triplicate. b Rf: Resistance-fold was calculated by dividing the IC50 values of ABC transporter overexpressing cells by the IC50 of the corresponding parental cells in the presence of mitoxantrone or tivantinib and in the absence of Ko143. * p < 0.05.