Table 1.
Effects of tivozanib on ABCB1-mediated drug resistance to paclitaxel, vinblastine and colchicine in KB-3-1 and KB-C2 cell lines.
| IC50 ± SD†; nM (resistance fold) | ||
|---|---|---|
| Paclitaxel | 6.5 ± 1.3 (1.0)‡ | 4931.4 ± 244.5 (763.4) |
| Paclitaxel +tivozanib 2.5 μM | 5.4 ± 2.6 (0.8) | 362.4 ± 83.2 (56.1)** |
| Paclitaxel + tivozanib 5 μM | 8.9 ± 1.7 (1.4) | 246.2 ± 77.9 (38.1)** |
| Paclitaxel + verapamil 5 μM | 6.7 ± 1.6 (1.0) | 8.7 ± 3.2 (1.4)** |
| Vinblastine | 0.2 ± 0.01 (1.0)‡ | 34.4 ± 1.6 (162.2) |
| Vinblastine + tivozanib 2.5 μM | 0.2 ± 0.03 (1.1) | 1.2 ± 0.4 (5.7)* |
| Vinblastine + tivozanib 5 μM | 0.2 ± 0.05 (1.2) | 0.2 ± 0.04 (1.1)* |
| Vinblastine + verapamil 5 μM | 0.2 ± 0.01 (0.8) | 0.2 ± 0.06 (1.1)* |
| Colchicine | 19.0 ± 3.4 (1.0)‡ | 8544.6 ± 603.0 (495.0) |
| Colchicine + tivozanib 2.5 μM | 20.8 ± 1.2 (1.1) | 6739.7 ± 211.7 (354.7)* |
| Colchicine + tivozanib 5 μM | 20.4 ± 1.7 (1.1) | 421.2 ± 25.0 (22.2)** |
| Colchicine + verapamil 5 μM | 19.1 ± 1.1 (1.0) | 684.2 ± 12.2 (36.0)** |
| Cisplatin | 2893.7 ± 223.1 (1.0)‡ | 3158.8 ± 433.2 (1.1) |
| Cisplatin + tivozanib 2.5 μM | 2727.8 ± 291.4 (1.0) | 2916.5 ± 354.4 (1.0) |
| Cisplatin + tivozanib 5 μM | 2614.7 ± 206.1 (1.0) | 3091.8 ± 514.3 (1.1) |
| Cisplatin + verapamil 5 μM | 2765.1 ± 141.4 (1.0) | 2661.0 ± 244.2 (0.9) |
†
Values represent the mean ± SD of at least three independent experiments, each performed in triplicate.
‡
Resistance fold was calculated by dividing the IC50 values of paclitaxel, vinblastine, colchicine or cisplatin of KB-C2 cells in the presence or absence of reversal agents by the IC50 values of substrates of the KB-3–1 cell line.
*
p < 0.05;
**
p < 0.01.
SD: Standard deviation.