Table 3.
The reversal efficacy of ARRY-334543 in ABCC1- and ABCC10-mediated drug resistance.
| IC50 ± SDa (μM) | ||||||
|---|---|---|---|---|---|---|
| Compounds | HEK293/pcDNA3.1 | (RF)b | HEK/ABCB1 | (RF)b | HEK/ABCC10 | (RF)b |
| Vincristine (μM) | 0.0122 ± 0.0010 | 1.0 | 0.1706 ± 0.0145 | 14.0 | 0.0914 ± 0.0078 | 7.5 |
| +ARRY-334543 0.25 μM | 0.0117 ± 0.0006 | 1.0 | 0.1621 ± 0.0089 | 13.3 | 0.0822 ± 0.0045 | 6.8 |
| +ARRY-334543 1.0 μM | 0.0118 ± 0.0008 | 1.0 | 0.1279 ± 0.0083 | 10.5 | 0.0366 ± 0.0024* | 3.0 |
| + Verapamil 5.0 μM | 0.0111 ± 0.0007 | 0.9 | 0.0146 ± 0.0008* | 1.2 | ||
| + Cepharanthine 2.5 μM | 0.0115 ± 0.0009 | 0.9 | 0.0171 ± 0.0011* | 1.4 | ||
| Cisplatin (μM) | 1.7059 ± 0.1347 | 1.0 | 1.6547 ± 0.0767 | 1.0 | 1.7912 ± 0.1185 | 1.1 |
| +ARRY-334543 1.0 μM | 1.6125 ± 0.0771 | 0.9 | 1.4996 ± 0.0563 | 0.9 | 1.7738 ± 0.0864 | 1.0 |
| + Verapamil 5.0 μM | 1.6550 ± 0.0999 | 1.0 | 1.5722 ± 0.0849 | 0.9 | ||
| + Cepharanthine 2.5 μM | 1.6749 ± 0.1046 | 1.0 | 1.5722 ± 0.0956 | 0.9 | ||
a
IC50 values are represented the mean ± standard deviation (SD).
b
Resistance fold (RF) was calculated by the IC50 values for vincristine or cisplatin of HEK293/pcDNA3.1 cell with ARRY-334543 or known reversing agents, or the resistant cell lines in the presence or absence of ARRY-334543 or reversing agents, divided by the IC50 values for vincristine or cisplatin of HEK293/pcDNA3.1 without the reversing agents.
*
P < 0.05, versus the control group.