Table 1.
The effect of MY-5445 on drug resistance mediated by ABCB1, ABCC1 or ABCG2 in HEK293 cells transfected with human ABCB1, ABCC1 or ABCG2
| Treatment | Concentration (μM) | Mean IC50 † ± SD and (FR‡) | |
|
| |||
| pcDNA-HEK293 (parental) [nM] | MDR19-HEKS293 (resistant) [nM] | ||
|
| |||
| Colchicine | - | 10.61±3.64 (1.0) | 256.55±55.25 (1.0) |
| + MY-5445 | 0.5 | 10.29±3.13 (1.0) | 247.39±49.20 (1.0) |
| + MY-5445 | 1.0 | 10.93±3.78 (1.0) | 266.45±64.09 (1.0) |
| + MY-5445 | 2.0 | 10.66±3.26 (1.0) | 314.17±66.13 (0.8) |
| + MY-5445 | 3.0 | 10.90±3.43 (1.0) | 355.55±81.95 (0.7) |
| + Tariquidar | 1.0 | 9.15±3.20 (1.2) | 11.10±3.48** (23.1) |
|
| |||
| pcDNA-HEK293 (parental) [nM] | MRP1-HEKS293 (resistant) [μM] | ||
|
| |||
| Etoposide | - | 273.20±63.61 (1.0) | 85.90±14.30 (1.0) |
| + MY-5445 | 0.5 | 212.02±36.82 (1.3) | 96.82±19.56 (0.9) |
| + MY-5445 | 1.0 | 260.10±48.11 (1.1) | 84.35±19.48 (1.0) |
| + MY-5445 | 2.0 | 293.37±54.28 (0.9) | 74.07±11.95 (1.2) |
| + MY-5445 | 3.0 | 231.90±39.99 (1.2) | 62.81±12.66 (1.4) |
| + MK-571 | 25.0 | 208.20±44.29 (1.3) | 9.13±1.69*** (9.4) |
|
| |||
| pcDNA-HEK293 (parental) [nM] | R482-HEKS293 (resistant) [nM] | ||
|
| |||
| Mitoxantrone | - | 2.44±0.27 (1.0) | 177.66±19.11 (1.0) |
| + MY-5445 | 0.5 | 2.01±0.30 (1.2) | 59.01±6.75*** (3.0) |
| + MY-5445 | 1.0 | 2.05±0.27 (1.2) | 25.87±3.17*** (6.9) |
| + MY-5445 | 2.0 | 2.01±0.27 (1.2) | 16.75±2.90*** (10.6) |
| + MY-5445 | 3.0 | 1.95±0.28 (1.3) | 13.54±2.17*** (13.1) |
| + Ko143 | 1.0 | 1.97±0.27 (1.2) | 12.91±2.16*** (13.8) |
| SN-38 | - | 3.14±0.80 (1.0) | 134.24±19.32 (1.0) |
| + MY-5445 | 0.5 | 3.31±0.90 (0.9) | 39.28±7.39** (3.4) |
| + MY-5445 | 1.0 | 2.93±0.68 (1.1) | 22.24±4.32*** (6.0) |
| + MY-5445 | 2.0 | 3.24±0.80 (1.0) | 15.30±3.44*** (8.8) |
| + MY-5445 | 3.0 | 3.31±0.69 (0.9) | 11.92±3.15*** (11.3) |
| + Ko143 | 1.0 | 2.59±0.60 (1.2) | 2.94±0.62*** (45.7) |
| Topotecan | - | 36.50±7.60 (1.0) | 384.96±31.52 (1.0) |
| + MY-5445 | 0.5 | 34.82±6.79 (1.0) | 101.64±13.01*** (3.8) |
| + MY-5445 | 1.0 | 33.51±7.37 (1.1) | 51.35±9.50*** (7.5) |
| + MY-5445 | 2.0 | 38.76±8.90 (0.9) | 32.99±6.14*** (11.7) |
| + MY-5445 | 3.0 | 37.19±9.21 (1.0) | 31.51±7.08*** (12.2) |
| + Ko143 | 1.0 | 37.06±8.52 (1.0) | 40.39±9.16*** (9.5) |
Abbreviation: FR, fold-reversal.
†
IC50 values are mean ± SD obtained from dose-response curves of at least three independent experiments using cytotoxicity assay as described in Materials and methods.
‡
FR values were calculated by dividing IC50 values of cells treated with a particular anticancer drug in the absence of an inhibitor by IC50 values of cells treated with the same anticancer drug in the presence of an inhibitor.
**
P<0.01;
***
P<0.001.