Table 3.
VS-4718 sensitized ABCG2-substrate-selected resistant cells to ABCG2 substrates.
| Treatment | IC50 ±SDa (RFb) | |||
|---|---|---|---|---|
| NCI-H460 (μM) | NCI-H460/MX20 (μM) | S1 (μM) | S1-M1-80 (μM) | |
| Mitoxantrone | 0.036 ± 0.008 (1.00) | 4.361 ± 0.609 (120.30) | 0.032 ± 0.002 (1.00) | 4.559 ± 1.607 (143.23) |
| +VS-4718 (1 μM) | 0.037 ± 0.013 (1.01) | 1.247 ± 0.456 (34.40)* | 0.029 ± 0.006 (0.91) | 2.098 ± 0.916 (65.90)* |
| +VS-4718 (3 μM) | 0.030 ± 0.015 (0.82) | 0.496 ± 0.193 (13.68)* | 0.027 ± 0.004 (0.85) | 0.577 ± 0.182 (18.12)* |
| +Ko 143 (3 μM) | 0.022 ± 0.006 (0.62) | 0.302 ± 0.018 (8.32)* | 0.026 ± 0.005 (0.81) | 0.034 ± 0.015 (1.08)* |
| SN-38 | 0.038 ± 0.012 (1.00) | 3.169 ± 0.493 (83.51) | 0.043 ± 0.003 (1.00) | 3.628 ± 1.819 (85.36) |
| +VS-4718 (1 μM) | 0.031 ± 0.013 (0.82) | 0.436 ± 0.287 (11.49)* | 0.041 ± 0.009 (0.95) | 0.365 ± 0.026 (8.59)* |
| +VS-4718 (3 μM) | 0.030 ± 0.012 (0.78) | 0.071 ± 0.015 (1.88)* | 0.053 ± 0.006 (1.25) | 0.097 ± 0.042 (2.27)* |
| +Ko 143 (3 μM) | 0.031 ± 0.021 (0.81) | 0.039 ± 0.003 (1.02)* | 0.052 ± 0.013 (1.21) | 0.045 ± 0.035 (1.05)* |
| Topotecan | 0.067 ± 0.009 (1.00) | 4.471 ± 0.644 (66.85) | 0.064 ± 0.007 (1.00) | 4.940 ± 0.701 (77.79) |
| +VS-4718 (1 μM) | 0.058 ± 0.034 (0.87) | 1.170 ± 0.398 (17.50)* | 0.061 ± 0.001 (0.95) | 1.801 ± 0.791 (28.36)* |
| +VS-4718 (3 μM) | 0.053 ± 0.026 (0.79) | 0.503 ± 0.053 (7.53)* | 0.057 ± 0.002 (0.90) | 0.434 ± 0.120 (6.84)* |
| +Ko 143 (3 μM) | 0.034 ± 0.013 (0.71) | 0.264 ± 0.034 (3.94)* | 0.051 ± 0.029 (0.80) | 0.306 ± 0.037 (4.81)* |
| Cisplatin | 1.658 ± 0.261 (1.00) | 1.696 ± 0.300 (1.02) | 1.447 ± 0.064 (1.00) | 1.508 ± 0.159 (1.04) |
| +VS-4718 (1 μM) | 2.024 ± 0.421 (1.22) | 1.672 ± 0.271 (1.01) | 1.347 ± 0.196 (0.93) | 1.873 ± 0.202 (1.29) |
| +VS-4718 (3 μM) | 1.550 ± 1.055 (0.93) | 1.699 ± 0.245 (1.02) | 1.290 ± 0.051 (0.89) | 1.840 ± 0.744 (1.27) |
| +Ko 143 (3 μM) | 1.812 ± 0.801 (1.09) | 1.721 ± 0.245 (1.04) | 1.417 ± 0.188 (0.98) | 1.506 ± 0.441 (1.04) |
a
IC50 values were determined by MTT assay as described in “Materials and Methods,”and were obtained from three independent experiments in triplicate.
b
Resistance fold (RF) was calculated from dividing the IC50 values of resistant cells (NCI-H460/MX20 and S1-M1-80) by the IC50 of parental cells (NCI-H460 and S1) in the presence or absence of VS-4718 or positive control inhibitor.
*
indicates p < 0.05 vs. group treated with antineoplastic drug only.