Table 2.
Effects of tivozanib on drug resistance to paclitaxel, vincristine and colchicine in HEK293/pcDNA3.1 and HEK/ABCB1 cell lines.
| IC50 ± SD†; nM (resistance fold) | ||
|---|---|---|
| Paclitaxel | 28.3 ± 4.3 (1.0)‡ | 8483.1 ± 726.4 (296.2) |
| Paclitaxel + tivozanib 2.5 μM | 21.9 ± 4.1 (0.8) | 1296.8 ± 383.4 (59.2)* |
| Paclitaxel + tivozanib 5 μM | 24.9 ± 3.7 (0.9) | 277.2 ± 44.7 (9.8)** |
| Paclitaxel + verapamil 5 μM | 20.0 ± 4.0 (0.7) | 26.8 ± 3.4 (0.9)** |
| Vincristine | 4.1 ± 0.9 (1.0)‡ | 1413.9 ± 159.7 (344.6) |
| Vincristine + tivozanib 2.5 μM | 3.6 ± 0.9 (0.9) | 751.1 ± 31.9 (183.2)* |
| Vincristine + tivozanib 5 μM | 3.8 ± 0.7 (0.9) | 44.8 ± 9.1 (10.9)** |
| Vincristine + verapamil 5 μM | 3.6 ± 0.6 (0.9) | 4.3 ± 2.8 (1.0)** |
| Colchicine | 20.4 ± 3.1 (1.0)‡ | 552.4 ± 66.2 (27.1) |
| Colchicine + tivozanib 2.5 μM | 24.8 ± 4.2 (1.2) | 381.6 ± 59.1 (18.7)* |
| Colchicine + tivozanib 5 μM | 23.5 ± 1.3 (1.2) | 125.1 ± 26.1 (6.1)* |
| Colchicine + verapamil 5 μM | 20.0 ± 1.5 (1.0) | 128.9 ± 16.2 (6.3)* |
| Cisplatin | 2914.2 ± 235.6 (1.0)‡ | 2251.6 ± 172.0 (0.8) |
| Cisplatin + tivozanib 2.5 μM | 3037.1 ± 273.2 (1.0) | 2233.0 ± 189.3 (0.8) |
| Cisplatin + tivozanib 5 μM | 2873.7 ± 352.7 (1.0) | 2211.1 ± 160.8 (0.8) |
| Cisplatin + verapamil 5 μM | 2671.1 ± 161.5 (1.0) | 2649.4 ± 293.6 (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, vincristine, colchicine or cisplatin of HEK/ABCB1 cells in the presence or absence of reversal agents by the IC50 values of substrates of the HEK293/pcDNA3.1 cell line.
*
p < 0.05;
**
p < 0.01.
SD: Standard deviation.