Table 1.
Effect of BBA on Reversing P-gp-Mediated Drug Resistance
| IC50 ± SDa (μM) (fold-reversal)b |
||||
|---|---|---|---|---|
| HepG2 | HepG2/ADM | MCF-7 | MCF-7/ADR | |
| doxorubicin | 0.3809 ± 0.0333 (1.00) | 85.3891 ± 2.9511 (1.00) | 0.2437 ± 0.0267 (1.00) | 17.1000 ± 0.8839 (1.00) |
| + BBA 0.625 μM | 0.3611 ± 0.0030 (1.05) | 21.6396 ± 1.2168 (3.95) | 0.2414 ± 0.0106 (1.01) | 4.1837 ± 0.4922 (4.09) |
| + BBA 1.25 μM | 0.3255 ± 0.0228 (1.17) | 6.0008 ± 0.0541 (14.23) | 0.2220 ± 0.0393 (1.10) | 2.3363 ± 0.3107 (7.32) |
| + BBA 2.5 μM | 0.3261 ± 0.0326 (1.17) | 3.6789 ± 0.3552 (23.21) | 0.2472 ± 0.0251 (0.99) | 1.2590 ± 0.1754 (13.58) |
| + BBA 5 μM | 0.3190 ± 0.0079 (1.19) | 1.5932 ± 0.0180 (53.60) | 0.1997 ± 0.0231 (1.22) | 0.6982 ± 0.0754 (24.49) |
| + verapamil 5 μM | 0.2989 ± 0.0345 (1.27) | 4.6455 ± 0.0487 (18.38) | 0.1693 ± 0.0343 (1.44) | 2.6930 ± 0.2222 (6.35) |
| vincristine | 0.0149 ± 0.0093 (1.00) | 2.6260 ± 0.1231 (1.00) | 0.0094 ± 0.0001 (1.00) | 0.7423 ± 0.0183 (1.00) |
| + BBA 0.625 μM | 0.0168 ± 0.0086 (0.88) | 0.7426 ± 0.0564 (3.54) | 0.0093 ± 0.0007 (1.01) | 0.0898 ± 0.0062 (8.23) |
| + BBA 1.25 μM | 0.0127 ± 0.0064 (1.17) | 0.2677 ± 0.0357 (9.81) | 0.0088 ± 0.0008 (1.06) | 0.0326 ± 0.0026 (22.80) |
| + BBA 2.5 μM | 0.0170 ± 0.0081 (0.87) | 0.0676 ± 0.0086 (38.88) | 0.0094 ± 0.0008 (1.00) | 0.0119 ± 0.0013 (62.59) |
| + BBA 5 μM | 0.0128 ± 0.0049 (1.16) | 0.0199 ± 0.0037 (132.29) | 0.0065 ± 0.0002 (1.45) | 0.0049 ± 0.0004 (151.04) |
| + verapamil 5 μM | 0.0108 ± 0.0077 (1.38) | 0.1193 ± 0.0407 (22.01) | 0.0050 ± 0.0006 (1.88) | 0.0252 ± 0.0028 (29.48) |
| paclitaxel | 0.0019 ± 0.0002 (1.00) | 1.5010 ± 0.0447 (1.00) | 0.0023 ± 0.0005 (1.00) | 0.7186 ± 0.0465 (1.00) |
| + BBA 0.625 μM | 0.0019 ± 0.0002 (1.01) | 0.9099 ± 0.0337 (1.65) | 0.0023 ± 0.0008 (1.00) | 0.1273 ± 0.0117 (5.65) |
| + BBA 1.25 μM | 0.0022 ± 0.0002 (0.86) | 0.3705 ± 0.0298 (4.05) | 0.0020 ± 0.0007 (1.15) | 0.0319 ± 0.0018 (22.54) |
| + BBA 2.5 μM | 0.0014 ± 0.0002 (1.35) | 0.0862 ± 0.0097 (17.42) | 0.0020 ± 0.0003 (1.15) | 0.0168 ± 0.0023 (42.72) |
| + BBA 5 μM | 0.0011 ± 0.0001 (1.72) | 0.0191 ± 0.0016 (78.59) | 0.0019 ± 0.0005 (1.25) | 0.0048 ± 0.0004 (151.07) |
| + verapamil 5 μM | 0.0016 ± 0.0002 (1.18) | 0.1419 ± 0.0150 (10.58) | 0.0022 ± 0.0004 (1.05) | 0.0121 ± 0.0021 (59.32) |
| cisplatin | 5.2585 ± 0.6399 (1.00) | 7.1703 ± 0.7670 (1.00) | 10.5700 ± 1.5712 (1.00) | 9.0415 ± 0.1110 (1.00) |
| + BBA 5 μM | 5.5675 ± 0.0799 (1.29) | 7.5537 ± 1.0330 (0.95) | 11.9433 ± 1.0310 (0.89) | 9.8800 ± 1.7112 (0.92) |
| + verapamil 5 μM | 5.5405 ± 0.3613 (1.29) | 7.4770 ± 0.8122 (0.96) | 10.2740 ± 1.0080 (1.03) | 9.1560 ± 1.2785 (0.99) |
| IC50 ± SDa (nM) (fold-reversal)b |
||||
| KB-3–1 | KB-C2 | HEK293 | HEK293/ABCB1 | |
| vincristine | 8.95 ± 0.69 (1.00) | 897.10 ± 80.45 (1.00) | 10.20 ± 0.89 (1.00) | 755.35 ± 60.57 (1.00) |
| + BBA 1.25 μM | 9.52 ± 0.81 (0.94) | 645.38 ± 117.05 (1.39) | 10.15 ± 0.90 (1.00) | 293.56 ± 28.76 (2.57) |
| + BBA 2.5 μM | 8.49 ± 0.11 (1.05) | 266.28 ± 93.54 (3.37) | 9.53 ± 0.71 (1.07) | 42.67 ± 3.76 (17.70) |
| + BBA 5 μM | 8.34 ± 0.74 (1.07) | 71.73 ± 13.62 (12.51) | 9.21 ± 1.12 (1.11) | 24.65 ± 2.73 (30.64) |
| + verapamil 5 μM | 5.91 ± 0.46 (1.51) | 74.07 ± 5.17 (12.11) | 8.90 ± 0.87 (1.15) | 17.91 ± 1.89 (42.17) |
| vinblastine | 53.26 ± 10.09 (1.00) | 1808.59 ± 18.55 (1.00) | 13.87 ± 1.28 (1.00) | 301.58 ± 27.22 (1.00) |
| + BBA 1.25 μM | 55.32 ± 8.74 (0.96) | 1761.98 ± 112.44 (1.03) | 13.15 ± 1.39 (1.05) | 106.12 ± 13.89 (2.84) |
| + BBA 2.5 μM | 49.57 ± 3.52 (1.07) | 796.84 ± 18.70 (2.27) | 12.89 ± 1.37 (1.08) | 34.93 ± 4.21 (8.63) |
| + BBA 5 μM | 70.09 ± 7.59 (0.76) | 146.22 ± 18.16 (12.37) | 13.32 ± 1.06 (1.04) | 16.82 ± 1.71 (17.93) |
| + verapamil 5 μM | 25.19 ± 2.64 (2.11) | 86.05 ± 5.33 (21.02) | 11.37 ± 0.95 (1.22) | 16.30 ± 1.60 (18.50) |
| paclitaxel | 6.79 ± 0.11 (1.00) | 2840.71 ± 549.87 (1.00) | 4.19 ± 0.32 (1.00) | 157.20 ± 13.07 (1.00) |
| + BBA 1.25 μM | 6.39 ± 0.13 (1.06) | 2377.54 ± 340.53 (1.19) | 3.99 ± 0.41 (1.05) | 40.45 ± 4.64 (3.89) |
| + BBA 2.5 μM | 6.93 ± 0.10 (0.98) | 1971.65 ± 275.33 (1.44) | 3.79 ± 0.35 (1.11) | 21.75 ± 1.96 (7.23) |
| + BBA 5 μM | 7.72 ± 0.15 (0.88) | 277.48 ± 15.12 (10.24) | 3.91 ± 0.37 (1.07) | 12.11 ± 1.28 (12.98) |
| + verapamil 5 μM | 6.49 ± 0.47 (1.05) | 131.89 ± 9.89 (21.54) | 3.52 ± 0.25 (1.19) | 15.93 ± 1.34 (9.87) |
| cisplatin | 3056.33 ± 323.51 (1.00) | 2840.44 ± 358.52 (1.00) | 2208.82 ± 82.24 (1.00) | 2526.16 ± 70.69 (1.00) |
| + BBA 5 μM | 4800.12 ± 208.38 (0.64) | 4939.01 ± 260.35 (0.58) | 2067.82 ± 93.44 (1.07) | 2370.29 ± 151.77 (1.07) |
| + verapamil 5 μM | 3035.92 ± 528.93 (1.01) | 3821.76 ± 249.19 (0.74) | 2511.15 ± 48.79 (0.88) | 2651.52 ± 99.08 (0.95) |
a
Data in the table are shown as the means ± SD of at least three independent experiments performed in triplicate.
b
The fold-reversals are calculated as IC50 for cells with the anticancer drug in the absence of inhibitors divided by that in the presence of inhibitors.