Compound | IC50 ± SD μM (fold-reversal) | Fold-resistance | |||
---|---|---|---|---|---|
KB | KBv200(ABCB1) | ||||
Doxorubicin | 0.0346 ± 0.0061 | (1.00) | 2.9903 ± 0.3484 | (1.00) | 86.4 |
 + 1.25 μM FW-04-806 | 0.0360 ± 0.0086 | (0.96) | 1.1805 ± 0.3313** | (2.53) |  |
 + 2.5 μM FW-04-806 | 0.0312 ± 0.0045 | (1.11) | 0.5546 ± 0.2563** | (5.39) |  |
 + 5 μM FW-04-806 | 0.0341 ± 0.0197 | (1.01) | 0.4107 ± 0.0603** | (7.28) |  |
 + 10 μM Verapamil | 0.0406 ± 0.01140 | (0.85) | 0.4147 ± 0.1578** | (7.21) |  |
Vincristine | 0.0039 ± 0.0001 | (1.00) | 4.4343 ± 0.8370 | (1.00) | 1335.9 |
 + 1.25 μM FW-04-806 | 0.0046 ± 0.0000 | (0.84) | 0.1236 ± 0.0325** | (35.87) |  |
 + 2.5 μM FW-04-806 | 0.0039 ± 0.0000 | (0.98) | 0.0518 ± 0.0113** | (85.64) |  |
 + 5 μM FW-04-806 | 0.0030 ± 0.0000 | (1.30) | 0.0156 ± 0.0034** | (284.86) |  |
 + 10 μM Verapamil | 0.0030 ± 0.0002 | (1.31) | 0.0637 ± 0.0122** | (69.62) |  |
Paclitaxel | 0.0023 ± 0.0018 | (1.00) | 3.9227 ± 2.3426 | (1.00) | 1705.5 |
 + 1.25 μM FW-04-806 | 0.0026 ± 0.0006 | (0.90) | 0.1044 ± 0.0474* | (37.59) |  |
 + 2.5 μM FW-04-806 | 0.0028 ± 0.0006 | (0.81) | 0.0457 ± 0.0042* | (85.80) |  |
 + 5 μM FW-04-806 | 0.0017 ± 0.0001 | (1.38) | 0.0127 ± 0.0038* | (308.55) |  |
 + 10 μM Verapamil | 0.0026 ± 0.0003 | (0.88) | 0.0688 ± 0.0394* | (57.06) |  |
 | K562 | K562/adr (ABCB1) |  | ||
Doxorubicin | 0.0382 ± 0.0002 | (1.00) | 5.1410 ± 1.8822 | (1.00) | 134.6 |
 + 1.25 μM FW-04-806 | 0.0283 ± 0.0006 | (1.35) | 5.8430 ± 1.1266 | (0.88) |  |
 + 2.5 μM FW-04-806 | 0.0307 ± 0.0011 | (1.25) | 2.0657 ± 0.9445 | (2.49) |  |
 + 5 μM FW-04-806 | 0.0372 ± 0.0027 | (1.03) | 0.5321 ± 0.0667* | (9.66) |  |
 + 10 μM Verapamil | 0.0402 ± 0.0019 | (0.95) | 0.7843 ± 0.1870* | (6.55) |  |
Vincristine | 0.0007 ± 0.0000 | (1.00) | 0.1708 ± 0.0051 | (1.00) | 244.0 |
 + 1.25 μM FW-04-806 | 0.0007 ± 0.0000 | (1.03) | 0.0368 ± 0.0027** | (4.65) |  |
 + 2.5 μM FW-04-806 | 0.0006 ± 0.0000 | (1.19) | 0.0193 ± 0.0012** | (8.84) |  |
 + 5 μM FW-04-806 | 0.0007 ± 0.0000 | (1.09) | 0.0040 ± 0.0001** | (43.04) |  |
 + 10 μM Verapamil | 0.0006 ± 0.0000 | (1.18) | 0.0027 ± 0.0002** | (64.21) |  |
Paclitaxel | 0.0068 ± 0.0002 | (1.00) | 0.6002 ± 0.0175 | (1.00) | 88.3 |
 + 1.25 μM FW-04-806 | 0.0072 ± 0.0001 | (0.94) | 0.1401 ± 0.0014** | (4.28) |  |
 + 2.5 μM FW-04-806 | 0.0066 ± 0.0002 | (1.02) | 0.0707 ± 0.0011** | (8.49) |  |
 + 5 μM FW-04-806 | 0.0060 ± 0.0001 | (1.12) | 0.0253 ± 0.0013** | (23.76) |  |
 + 10 μM Verapamil | 0.0072 ± 0.0001 | (0.93) | 0.0335 ± 0.0004** | (17.92) |  |
 | MCF-7 | MCF-7/adr (ABCB1) |  | ||
Doxorubicin | 0.1653 ± 0.0066 | (1.00) | 8.9867 ± 0.8227 | (1.00) | 54.4 |
 + 1.25 μM FW-04-806 | 0.2010 ± 0.0397 | (0.82) | 2.0513 ± 0.1232** | (4.38) |  |
 + 2.5 μM FW-04-806 | 0.1870 ± 0.0608 | (0.88) | 0.8483 ± 0.0740** | (10.59) |  |
 + 5 μM FW-04-806 | 0.2215 ± 0.0486 | (0.75) | 0.4863 ± 0.0086** | (18.48) |  |
 + 10 μM Verapamil | 0.1769 ± 0.0051 | (0.93) | 0.3688 ± 0.0460** | (24.37) |  |
 | HEK293/pcDNA3.1 | HEK293/ABCB1 |  | ||
Doxorubicin | 0.0836 ± 0.0001 | (1.00) | 1.7513 ± 0.0875 | (1.00) | 20.9 |
 + 2.5 μM FW-04-806 | 0.0794 ± 0.0017 | (1.05) | 0.2881 ± 0.0077** | (6.08) |  |
 + 5 μM FW-04-806 | 0.0726 ± 0.0005 | (1.15) | 0.1479 ± 0.0036** | (11.84) |  |
 + 10 μM FW-04-806 | 0.0879 ± 0.0004 | (0.95) | 0.1467 ± 0.0055** | (11.94) |  |
 + 10 μM Verapamil | 0.0681 ± 0.0005 | (1.23) | 0.1868 ± 0.0002** | (9.37) |  |
 | S1 | S1-MI-80(ABCG2) |  | ||
Mitoxantrone | 0.0409 ± 0.0007 | (1.00) | 48.7067 ± 5.6101 | (1.00) | 1190.9 |
 + 2.5 μM FW-04-806 | 0.0426 ± 0.0008 | (0.96) | 23.2267 ± 1.9806** | (2.10) |  |
 + 5 μM FW-04-806 | 0.0446 ± 0.0019 | (0.92) | 20.3067 ± 2.7537** | (2.40) |  |
 + 10 μM FW-04-806 | 0.0410 ± 0.0017 | (1.00) | 17.2100 ± 0.4694** | (2.83) |  |
 + 2.5 μM KO134 | 0.0483 ± 0.0075 | (0.85) | 0.3390 ± 0.0134** | (143.66) |  |
Topotecan | 0.6221 ± 0.0639 | (1.00) | 168.1667 ± 18.0736 | (1.00) | 270.3 |
 + 2.5 μM FW-04-806 | 0.5729 ± 0.1353 | (1.09) | 138.7333 ± 3.2716 | (1.21) |  |
 + 5 μM FW-04-806 | 0.4887 ± 0.0452 | (1.27) | 116.6667 ± 4.5170** | (1.44) |  |
 + 10 μM FW-04-806 | 0.5137 ± 0.0071 | (1.21) | 59.9400 ± 7.3335** | (2.81) |  |
 + 2.5 μM KO134 | 0.6414 ± 0.0178 | (0.97) | 11.7120 ± 2.9969** | (14.36) |  |
 | H460 | H460/MX20(ABCG2) |  | ||
Mitoxantrone | 0.0110 ± 0.0001 | (1.00) | 1.0716 ± 0.0644 | (1.00) | 97.4 |
 + 2.5 μM FW-04-806 | 0.0109 ± 0.0003 | (1.01) | 0.3994 ± 0.0127** | (2.68) |  |
 + 5 μM FW-04-806 | 0.0115 ± 0.0005 | (0.96) | 0.2630 ± 0.0097** | (4.08) |  |
 + 10 μM FW-04-806 | 0.0109 ± 0.0002 | (1.01) | 0.2254 ± 0.0057** | (4.75) |  |
 + 2.5 μM KO134 | 0.0114 ± 0.0006 | (0.97) | 0.1728 ± 0.0015** | (6.20) |  |
Topotecan | 0.0583 ± 0.0001 | (1.00) | 100.5367 ± 9.0013 | (1.00) | 1724.5 |
 + 2.5 μM FW-04-806 | 0.0591 ± 0.0015 | (0.99) | 66.9167 ± 1.1787** | (1.50) |  |
 + 5 μM FW-04-806 | 0.0582 ± 0.0002 | (1.00) | 53.4433 ± 7.4395** | (1.88) |  |
 + 10 μM FW-04-806 | 0.0546 ± 0.0004 | (1.07) | 38.3900 ± 3.9674** | (2.62) |  |
 + 2.5 μM KO134 | 0.0568 ± 0.0003 | (1.02) | 21.0567 ± 1.3238** | (4.77) |  |
 | HEK293/pcDNA3.1 | HEK293/ABCG2-R2 |  | ||
Mitoxantrone | 0.0054 ± 0.0006 | (1.00) | 0.4322 ± 0.0139 | (1.00) | 80.0 |
 + 1.25 μM FW-04-806 | 0.0035 ± 0.0000 | (1.55) | 0.2084 ± 0.0275** | (2.07) |  |
 + 2.5 μM FW-04-806 | 0.0059 ± 0.0001 | (0.91) | 0.1960 ± 0.0102** | (2.20) |  |
 + 5 μM FW-04-806 | 0.0034 ± 0.0001 | (1.59) | 0.1702 ± 0.0291** | (2.54) |  |
 + 2.5 μM KO134 | 0.0048 ± 0.0001 | (1.11) | 0.2990 ± 0.0009** | (1.45) |  |