Table 1.

The effect of ibrutinib on reversal of MRP1-mediated MDR in HEK293/pcDNA3.1 and HEK293/MRP1 cells

	IC50 ± SD (nM) (fold resistance)
Compounds	HEK293/pcDNA3.1	HEK293/MRP1
Vincristine	2.37 ± 0.67 (1.00)	21.7 ± 3.22 (9.16)
+Ibrutinib 1 μM	2.19 ± 0.40 (0.92)	8.39 ± 1.01 (3.54)**
+Ibrutinib 5 μM	1.84 ± 0.35 (0.78)	2.51 ± 0.55 (1.06)**
+MK571 50 μM	2.07 ± 0.32 (0.87)	4.21 ± 0.43 (1.78)**
Vinblastine	1.05 ± 0.20 (1.00)	6.92 ± 1.02 (6.59)
+Ibrutinib 1 μM	0.90 ± 0.11 (0.86)	3.45 ± 0.66 (3.29)**
+Ibrutinib 5 μM	0.80 ± 0.23 (0.76)	1.55 ± 0.21 (1.47)**
+MK571 50 μM	0.83 ± 0.39 (0.79)	2.39 ± 0.49 (2.28)**
Doxorubicin	21.3 ± 2.26 (1.00)	115 ± 7.93 (5.39)
+Ibrutinib 1 μM	20.7 ± 3.11 (0.97)	67.1 ± 8.40 (3.14)**
+Ibrutinib 5 μM	22.9 ± 1.76 (1.07)	27.8 ± 2.01 (1.30)**
+MK571 50 μM	21.9 ± 2.05 (1.03)	58.8 ± 5.29 (2.76)**
Cisplatin	1502 ± 120 (1.00)	1932 ± 200 (1.29)
+Ibrutinib 1 μM	1405 ± 200 (0.94)	1912 ± 125 (1.27)
+Ibrutinib 5 μM	1258 ± 179.50 (0.84)	1761 ± 220 (1.17)
+MK571 50 μM	1402 ± 210.38 (0.93)	1848 ± 176 (1.23)
Paclitaxel	7.03 ± 2.01 (1.00)	6.33 ± 1.41 (0.90)
+Ibrutinib 5 μM	6.11 ± 1.02 (0.87)	5.50 ± 1.34 (0.78)
+MK571 50 μM	5.84 ± 1.15 (0.83)	4.99 ± 1.44 (0.71)
5-FU	14 418. ± 21265 (1.00)	20 185 ± 3463 (1.40)
+Ibrutinib 5 μM	15 270 ± 3016 (1.06)	22 658 ± 4334 (1.57)
+MK571 50 μM	16 369 ± 2264 (1.14)	23 049 ± 5746 (1.60)

Cell survival was determined by MTT assays. Data shown are means ± SDs of at least 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 HEK293/MRP1 cells in the presence or absence of inhibitor, or HEK293/pcDNA3.1 cells with inhibitors, by the IC₅₀ of HEK293/pcDNA3.1 cells without inhibitor.

^*P < 0.05

^**P < 0.01 significantly different from values obtained in the absence of inhibitor.