Table 2.
The effect of ibrutinib on reversal of MRP1-mediated MDR in HL60 and HL60/Adr cells
| IC50 ± SD (nM) (fold resistance) | ||
|---|---|---|
| Compounds | HL60 | HL60/Adr |
| Vincristine | 12.6 ± 2.33 (1.00) | 2021 ± 191(161) |
| +Ibrutinib 1 μM | 13.2 ± 1.51 (1.05) | 900 ± 120 (72)** |
| +Ibrutinib 5 μM | 9.12 ± 2.82 (0.72) | 138 ± 11.3 (11.0)** |
| +MK571 50 μM | 10.5 ± 1.90 (0.83) | 190 ± 20.4 (15.1)** |
| Doxorubicin | 59.2 ± 14.90 (1.00) | 3890 ± 340 (65.8) |
| +Ibrutinib 1 μM | 52.3 ± 8.11 (0.88) | 1671 ± 210 (28.2)** |
| +Ibrutinib 5 μM | 48.1 ± 5.27 (0.81) | 624 ± 100 (10.6)** |
| +MK571 50 μM | 49.8 ± 4.56 (0.84) | 705 ± 70.4 (11.9)** |
| Cisplatin | 1804 ± 201 (1.00) | 2101 ± 321 (1.16) |
| +Ibrutinib 5 μM | 1726 ± 229 (0.96) | 2255 ± 219 (1.25) |
| +MK571 50 μM | 1623 ± 219 (0.90) | 2076 ± 302 (1.15) |
| Paclitaxel | 7.71 ± 1.02 (1.00) | 6.65 ± 1.20 (0.86) |
| +Ibrutinib 5 μM | 8.16 ± 1.45 (1.05) | 6.74 ± 0.89 (0.87) |
| +MK571 50 μM | 7.28 ± 2.10 (0.94) | 7.90 ± 1.48 (1.02) |
| 5-FU | 35 999 ± 4005 (1.00) | 38 037 ± 4185 (1.06) |
| +Ibrutinib 5 μM | 31 653 ± 5392 (0.88) | 39 627 ± 5205 (1.10) |
| +MK571 50 μM | 39 9757 ± 6198 (1.11) | 41 696 ± 5531 (1.16) |
Cell survival was determined by MTT assays. Data shown are means ± SDs of three independent experiments performed in triplicate. The fold resistance of MDR (values given in parentheses) was calculated by dividing the IC50 values of substrate in HL60/Adr cells in the absence or presence of inhibitor, or the IC50 values of substrate in HL60 cells with inhibitor, by IC50 of HL60 cells without inhibitor.
*
P < 0.05
**
P < 0.01 significantly different from values obtained in absence of inhibitor.