|
Compounds
|
IC50 ± SD, µmol/L (Fold reversal)
|
|---|
|
S1
|
S1-M1-80(ABCG2)
|
|---|
|
Topetecan
|
0.250 ± 0.014
|
(1.00)
|
12.79 ± 0.241
|
(1.00)
|
|
+0.25 µmol/L Axitinib
|
0.249 ± 0.020
|
(1.01)
|
6.692 ± 0.504b
|
(1.85)
|
|
+0.5 µmol/L Axitinib
|
0.255 ± 0.017
|
(0.98)
|
4.964 ± 0.320b
|
(2.47)
|
|
+ 1.0 µmol/L Axitinib
|
0.199 ± 0.006
|
(1.26)
|
3.020 ± 0.242b
|
(4.11)
|
|
+0.5 µmol/L FTC
|
0.244 ± 0.013
|
(1.02)
|
1.195 ± 0.108b
|
(10.7)
|
|
Mitoxantrone
|
0.193 ± 0.021
|
(1.00)
|
14.668 ± 0.636
|
(1.00)
|
|
+0.25 µmol/L Axitinib
|
0.194 ± 0.057
|
(0.99)
|
7.992 ± 0.675b
|
(1.84)
|
|
+0.5 µmol/L Axitinib
|
0.201 ± 0.011
|
(0.96)
|
4.140 ± 0.301b
|
(3.54)
|
|
+ 1.0 µmol/L Axitinib
|
0.185 ± 0.011
|
(1.12)
|
2.904 ± 0.482b
|
(5.05)
|
|
+0.5 µmol/L FTC
|
0.188 ± 0.011
|
(1.03)
|
1.272 ± 0.056b
|
(11.5)
|
|
Cisplatin
|
14.877 ± 1.126
|
(1.00)
|
14.496 ± 1.112
|
(1.00)
|
|
+ 1.0 µmol/L Axitinib
|
14.206 ± 1.460
|
(1.05)
|
14.360 ± 1.812
|
(1.01)
|
| |
KB
|
KBv200(ABCB1)
|
|
Doxorubicin
|
0.024 ± 0.002
|
(1.00)
|
2.204 ± 0.108
|
(1.00)
|
|
+0.25 µmol/L Axitinib
|
0.024 ± 0.002
|
(1.00)
|
2.022 ± 0.185
|
(1.08)
|
|
+0.5 µmol/L Axitinib
|
0.025 ± 0.001
|
(0.96)
|
2.153 ± 0.146
|
(1.02)
|
|
+ 1.0 µmol/L Axitinib
|
0.015 ± 0.004c
|
(1.63)
|
1.250 ± 0.215c
|
(1.76)
|
|
+ 10 µmol/L Verapamil
|
0.024 ± 0.003
|
(1.00)
|
0.109 ± 0.008b
|
(20.2)
|
|
Cispatin
|
1.552 ± 0.121
|
(1.00)
|
2.364 ± 0.241
|
(1.00)
|
|
+ 1.0 µmol/L Axitinib
|
1.514 ± 0.117
|
(1.03)
|
2.412 ± 0.225
|
(0.98)
|
| |
HL60
|
HL60/ADR(ABCC1)
|
|
Doxorubicin
|
0.055 ± 0.011
|
(1.00)
|
5.725 ± 0.203
|
(1.00)
|
|
+0.1 µmol/L Axitinib
|
0.054 ± 0.006
|
(1.02)
|
5.719 ± 0.591
|
(1.00)
|
|
+0.2 µmol/L Axitinib
|
0.056 ± 0.006
|
(0.98)
|
5.759 ± 0.659
|
(0.99)
|
|
+0.4 µmol/L Axitinib
|
0.049 ± 0.005
|
(1.13)
|
5.476 ± 0.384
|
(1.04)
|
|
+40 µmol/L MK571
|
0.054 ± 0.005
|
(1.02)
|
1.108 ± 0.182b
|
(5.17)
|
|
Cisplatin
|
1.456 ± 0.187
|
(1.00)
|
1.658 ± 0.118
|
(1.00)
|
|
+0.4 µmol/L Axitinib
|
1.516 ± 0.125
|
(0.96)
|
1.524 ± 0.175
|
(1.08)
|
| |
SW1573
|
SW1573/2R120(LRP)
|
|
Doxorubicin
|
0.108 ± 0.012
|
(1.00)
|
1.266 ± 0.121
|
(1.00)
|
|
+0.25 µmol/L Axitinib
|
0.096 ± 0.004
|
(1.12)
|
1.214 ± 0.174
|
(1.04)
|
|
+0.5 µmol/L Axitinib
|
0.098 ± 0.004
|
(1.10)
|
1.236 ± 0.122
|
(1.02)
|
|
+ 1.0 µmol/L Axitinib
|
0.094 ± 0.006
|
(1.14)
|
1.138 ± 0.088
|
(1.11)
|
|
Cisplatin
|
2.473 ± 0.167
|
(1.00)
|
9.659 ± 1.073
|
(1.00)
|
|
+ 1.0 µmol/L Axitinib
|
2.790 ± 0.147
|
(0.89)
|
9.180 ± 0.881
|
(1.05)
|
| |
NIH3T3
|
NIH3T3/MRP4-2(ABCC4)
|
|
6-MP
|
0.298 ± 0.050
|
(1.00)
|
11.852 ± 1.564
|
(1.00)
|
|
+0.25 µmol/L Axitinib
|
0.285 ± 0.034
|
(1.04)
|
11.145 ± 1.048
|
(1.06)
|
|
+0.5 µmol/L Axitinib
|
0.318 ± 0.045
|
(0.94)
|
10.709 ± 1.637
|
(1.11)
|
|
+ 1.0 µmol/L Axitinib
|
0.265 ± 0.011
|
(1.12)
|
12.319 ± 1.704
|
(0.96)
|
|
Cisplatin
|
6.140 ± 0.728
|
(1.00)
|
5.668 ± 0.690
|
(1.00)
|
|
+ 1.0 µmol/L Axitinib
|
5.033 ± 0.296
|
(1.21)
|
5.842 ± 0.691
|
(0.97)
|
- aCell survival was determined by MTT assays as described in Materials and Methods. Data are the mean ± standard deviation (SD) of at least three independent experiments performed in triplicate. The fold reversal of MDR (values given in parentheses) was calculated by dividing the IC50 for cells with the anticancer drugs in the absence of axitinib by that obtained in the presence of axitinib. bP < 0.01; cP < 0.05 versus the values obtained in the absence of inhibitor
