Table 1.
Ibrutinib enhances the effect of paclitaxel in ABCBl-overexpressinq cells
| Drugs | IC50 ± SDa (nmol/L; fold resistance) |
|
|---|---|---|
| KB-3–1 | KB-C2 | |
| Paclitaxel | 0.35 ± 0.02 (1.00)b | 38.91 ± 1.86 (111.17) |
| +Ibrutinib 1 μmol/L | 0.37 ± 0.05 (1.05) | 7.65 ± 0.92 (21.71)c |
| +Ibrutinib 2.5 μmol/L | 0.36 ± 0.06 (1.03) | 3.19 ± 0.53 (6.02)c |
| +Ibrutinib 5 μmol/L | 0.38 ± 0.07 (1.09) | 0.91 ± 0.08 (2.6)c |
| +Verapamil 5 μmol/L | 0.34 ± 0.03 (0.97) | 1.18 ± 0.19 (3.37)c |
| Cisplatin | 2,709.79 ± 226.25 (1.00)b | 2,276.11 ± 213.81 (0.84) |
| +Ibrutinib 1 μmol/L | 2,601.54 ± 331.01 (0.96) | 2,258.57 ± 195.83 (0.83) |
| +Ibrutinib 2.5 μmol/L | 2,507.75 ± 197.13 (0.93) | 2,251.71 ± 287.17 (0.83) |
| +Ibrutinib 5 μmol/L | 2,542.87 ± 231.55 (0.94) | 2,306.39 ± 248.05 (0.85) |
| +Verapamil 5 μmol/L | 2,721.24 ± 274.60 (1.00) | 2,358.20 ± 148.95 (0.87) |
| K562 | K562/AO2 | |
| Paclitaxel | 5.08 ± 0.62 (1.00) | 820.59 ± 71.03 (161.53) |
| +Ibrutinib (1 μmol/L) | 4.64 ± 0.59 (0.91) | 515.33 ± 66.21 (101.44)c |
| +Ibrutinib (2.5 μmol/L) | 4.74 ± 0.87 (0.93) | 184.67 ± 20.33 (36.35)c |
| +Verapamil (2.5 μmol/L) | 4.80 ± 0.48 (0.94) | 141.36 ± 18.91 (25.85)c |
| Cisplatin | 4,188.82 ± 400.43 (1.00) | 4,974.80 ± 400.32 (1.19) |
| +Ibrutinib (1 μmol/L) | 4,185.74 ± 200.05 (1.00) | 4,373.33 ± 698.68 (1.04) |
| +Ibrutinib (2.5 μmol/L) | 4,815.90 ± 759.21 (1.15) | 4,582.47 ± 600.09 (1.09) |
| +Verapamil (2.5 μmol/L) | 4,296.62 ± 459.60 (1.03) | 5,167.82 ± 600.31 (1.23) |
| HEK293/pcDNA3.1 | HEK293/ABCB1 | |
| Paclitaxel | 3.24 ± 0.51 (1.00)b | 545.00 ± 20.21 (168.21) |
| +Ibrutinib 1 μmol/L | 2.93 ± 0.41 (0.90) | 291.26 ± 31.39 (89.90)c |
| +Ibrutinib 2.5 μmol/L | 3.07 ± 0.65 (0.95) | 99.42 ± 11.44 (30.69)c |
| +Ibrutinib 5 μmol/L | 2.97 ± 0.53 (0.92) | 8.79 ± 1.76 (2.70)c |
| +Verapamil 5 μmol/L | 3.05 ± 0.39 (0.94) | 6.44 ± 1.23 (1.99)c |
| Cisplatin | 1,308.24 ± 132.33 (1.00)b | 1,142.00 ± 61.28 (0.87) |
| +Ibrutinib 1 μmol/L | 1,320.33 ± 146.49 (1.01) | 1,071.76 ± 36.89 (0.82) |
| +Ibrutinib 2.5 μmol/L | 1,369.42 ± 175.93 (1.05) | 1,211.95 ± 193.30 (0.93) |
| +Ibrutinib 5 μmol/L | 1,310.45 ± 128.63 (1.00) | 1,172.69 ± 147.66 (0.90) |
| +Verapamil 5 μmol/L | 1,260.24 ± 96.82 (0.96) | 1,236.06 ± 170.06 (0.94) |
NOTE: Cell survival was determined by MTT.
a
Values represent IC50 ± SD of at least three independent experiments performed in triplicate.
b
The fold reversal of MDR (values given in parentheses) was calculated by dividing the IC50 values of substrate in the resistant cells in the absence or presence of inhibitors, or the parent cells with inhibitors, by the IC50 of the parental cells without reversal agents.
c
P < 0.05, significantly different from values obtained in the absence of the reversal agents.