Table 2. A-803467 enhances the cytotoxicity of ABCG2 substrate anticancer drugs in H460/MX20 cells overexpressing ABCG2.
| Treatments | IC50 ± SD (nM) | ||||
|---|---|---|---|---|---|
| H460 | FR | H460/MX20 | FR | ||
| Mitoxantrone | 58.5 ± 4.2 | 1.0 | 7956.0 ± 198.2 | 135.9# | |
| +A-803467 (2.5 μM) | 57.9 ± 1.8 | 0.9 | 773.0 ± 18.9 | 13.2* | |
| +A-803467 (7.5 μM) | 55.2 ± 1.3 | 0.9 | 345.5 ± 16.7 | 5.9* | |
| +FTC (5 μM) | 55.3 ± 2.3 | 0.9 | 363.5 ± 18.7 | 6.2* | |
| Topotecan | 23.4 ± 0.8 | 1.0 | 1258.8 ± 47.4 | 53.3# | |
| +A-803467 (2.5 μM) | 20.9 ± 1.2 | 0.8 | 445.8 ± 24.7 | 19.0* | |
| +A-803467 (7.5 μM) | 19.3 ± 0.8 | 0.8 | 94.4 ± 5.2 | 4.0* | |
| +FTC (5 μM) | 19.7 ± 0.4 | 0.8 | 112.5 ± 8.2 | 4.8* | |
| Cisplatin | 2225.5 ± 12.3 | 1.0 | 2147.8 ± 24.3 | 0.9 | |
| +A-803467 (2.5 μM) | 2147 ± 24.3 | 0.9 | 2143.9 ± 42.2 | 0.9 | |
| +A-803467 (7.5 μM) | 2209.1 ± 42.3 | 0.9 | 2170 ± 72.1 | 0.9 | |
| +FTC (5 μM) | 2126.2 ± 50.9 | 0.9 | 2172.8 ± 49.9 | 0.9 | |
Data represents the mean IC50 values for each cell line ± SD obtained from three independent sets of experiments. Statistical analysis was performed by One-way ANOVA followed by Newman-Keuls Multiple Comparison Test. Statistical significance was set at P < 0.05.
*
P < 0.05 versus the control group.
#
P < 0.05 versus the control of H460 group. The fold resistance (FR) was determined by dividing the IC50 value of the anticancer drug for H460 and H460/MX20, in the absence or presence of reversal agents, by the IC50 value of the respective anticancer drug for H460, in the absence of reversal agent. FTC was used as a positive control of ABCG2 inhibitor.