Effect of Ko143 on the cytotoxicity of transporter-specific substrates in human cell lines
| Cell Line | Cytotoxic Drug | Cytotoxicity Value (IC50) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Drug Alone | Drug + 1 nM Ko143 | Drug + 10 nM Ko143 | Drug + 100 nM Ko143 | Drug + 1 μM Ko143 | Drug + 5 μM Ko143 | ||||||||
| IC50 | RR | IC50 | RR | IC50 | RR | IC50 | RR | IC50 | RR | IC50 | RR | ||
| nM | nM | nM | nM | nM | nM | ||||||||
| HEK ABCG2 | MTX | 138 ± 20 | 28 | 98 ± 8.3 | 20a | 54 ± 1 | 11b | 1 ± 0.3 | 0.2c | 2 ± 0 | 0.4c | 1.4 ± 0.3 | 0.3c |
| HEK PC | MTX | 5 ± 0 | |||||||||||
| HEK ABCB1 | Paclitaxel | 1243 ± 40 | 414 | — | — | 1205 ± 43 | 402 | 393 ± 37 | 131d | 67 ± 13 | 22d | ||
| HEK PC | Paclitaxel | 3 ± 1 | |||||||||||
| HEK ABCC1 | Doxo | 2481 ± 75 | 92 | — | — | 3136 ± 226 | 116b | 652 ± 292 | 24c | 222 ± 27 | 8d | ||
| HEK PC | Doxo | 27 ± 5 | |||||||||||
Doxo, doxorubicin; RR, resistance ratio (the quotient of the IC50 value of the resistant cell line to that of the parental line).
↵a P < 0.05 (α < 0.05, from initial IC50 value of resistant cell line) by Student’s two-tailed t test.
↵b P < 0.01 (α < 0.05, from initial IC50 value of resistant cell line) by Student’s two-tailed t test.
↵c P < 0.001 (α < 0.05, from initial IC50 value of resistant cell line) by Student’s two-tailed t test.
↵d P < 0.0001 (α < 0.05, from initial IC50 value of resistant cell line) by Student’s two-tailed t test.