Table 4.
The effect of linsitinib on reversal of ABCB1- and ABCC1-mediated MDR.
| Drugs | IC50 ± SDa (nM) (resistance fold) b |
|
|---|---|---|
| SW620 | SW620/AD300 | |
| Vincristine | 7.80 ± 0.08 (1.00) | 909.60 ± 8.91 (116.62) |
| +Linsitinib 1 μM | 7.06 ± 0.07 (0.91) | 885.08 ± 7.92 (113.47) |
| +Linsitinib 2 μM | 6.42 ± 0.09 (0.82) | 274.24 ± 22.88** (35.16) |
| +Verapamil 2 μM | 7.23 ± 0.11 (0.93) | 70.23 ± 9.40** (9.00) |
| HEK293/pcDNA3.1 | HEK293/ABCC1 | |
| Vincristine | 1.45 ± 0.20 (1.00) | 19.29 ± 2.08 (13.30) |
| +Linsitinib 1 μM | 1.41 ± 0.22 (0.97) | 19.86 ± 1.55 (13.70) |
| +Linsitinib 2 μM | 1.39 ± 0.17 (0.96) | 21.02 ± 2.10 (14.49) |
| +PAK-104P 2 μM | 1.20 ± 0.08 (0.83) | 3.83 ± 0.42** (2.64) |
a
IC50: concentration that inhibited cell survival by 50% (means ± SD).
b
Resistance-fold was determined by dividing the IC50 values of substrate in SW620/AD300 cells by the IC50 of substrate in SW620 cells in the absence of linsitinib; or the IC50 of substrate in SW620 cells in the presence of linsitinib divided by the IC50 of substrate in SW620 cells in the absence of linsitinib. The resistance-fold for HEK293/pcDNA3.1 and HEK293/ABCC1 cells was obtained in the similar manner. Values in table are means ± SD of three independent experiments performed in triplicate.
**
p < 0.01 versus that obtained in the absence of inhibitor.