Table 2.
The effect of linsitinib on reversal of ABCG2-mediated MDR in gene-transfected cell lines.
| Drugs | IC50 ± SDa (nM) (resistance fold)b |
|||
|---|---|---|---|---|
| HEK293/pcDNA3.1 | ABCG2-482-R2 | ABCG2-482-G2 | ABCG2-482-T7 | |
| Mitoxantrone | 24.27 ± 2.72 (1.00) | 170.58 ± 17.35 (7.03) | 234.93 ± 20.53 (9.68) | 232.59 ± 17.95 (9.58) |
| +Linsitinib 1 µM | 21.24 ± 2.94 (0.88) | 33.79 ± 3.75** (1.39) | 89.27 ± 59.90* (3.68) | 27.94 ± 1.84** (1.15) |
| +Linsitinib 2 µM | 17.78 ± 1.61 (0.73) | 14.12 ± 1.61** (0.58) | 23.15 ± 3.29** (0.95) | 76.81 ± 10.21 (824) |
| +FTC 2 µM | 21.67 ± 2.04 (0.89) | 14.55 ± 1.28** (0.60) | 15.80 ± 1.55** (0.65) | 104.47 ± 25.37** (4.30) |
| SN-38 | 9.32 ± 1.32 (1.00) | 122.99 ± 20.60 (13.20) | 146.93 ± 16.07 (15.77) | 25.65 ± 2.63** (1.06) |
| +Linsitinib 1 μM | 7.89 ± 0.78 (0.85) | 33.85 ± 3.16** (3.63) | 19.79 ± 1.66** (2.12) | 23.99 ± 1.40** (2.57) |
| +Linsitinib 2 μM | 6.69 ± 0.97 (0.72) | 9.47 ± 1.22** (1.02) | 10.07 ± 1.28** (1.08) | 10.30 ± 2.32** (1.11) |
| +FTC 2 μM | 6.76 ± 1.08 (0.73) | 9.70 ± 0.94** (1.04) | 9.07 ± 0.82** (0.97) | 9.74 ± 1.20** (1.05) |
| Cisplatin | 2450.39 ± 223.91 (1.00) | 1323.84 ± 120.22 (0.54) | 1684.76 ± 177.60 (0.69) | 1516.75 ± 180.73 (0.62) |
| +Linsitinib 2 μM | 2225.60 ± 301.60 (0.91) | 1219.85 ± 156.30 (0.50) | 1609.99 ± 153.07 (0.66) | 1690.92 ± 166.04 (0.69) |
a
IC50: concentration that inhibited cell survival by 50% (means ± SD).
b
Resistance-fold was determined by dividing the IC50 values of substrate in ABCG2–482-R2, ABCG2–482-T7 and ABCG2–482-G2 cells by the IC50 of substrate in HEK293/pcDNA3.1 cells in the absence of linsitinib; or the IC50 of substrate in HEK293/pcDNA3.1 cells in the presence of linsitinib divided by the IC50 of substrate in HEK293/pcDNA3.1 cells in the absence of linsitinib. Values in table are means ± SD of three independent experiments performed in triplicate.
*
p < 0.05,
**
p < 0.01 versus that obtained in the absence of inhibitor.