Table 1A.

Effect of osimertinib on reversing ABCB1- and ABCG2-mediated MDR in drug-selected cell lines

IC50 ± SD (μmol/L; fold-reversal)
CompoundsKBKBv200 (ABCB1)
VCR0.0020 ± 0.0003(1.00)0.5651 ± 0.0325(1.00)
 + 0.1 μmol/L osimertinib0.0019 ± 0.0002(1.05)0.1176 ± 0.0121 **(4.81)
 + 0.2 μmol/L osimertinib0.0018 ± 0.0004(1.11)0.0905 ± 0.0029 **(6.24)
 + 0.4 μmol/L osimertinib0.0018 ± 0.0005(1.11)0.0534 ± 0.0041 **(10.58)
 + 10 μmol/L VRP0.0017 ± 0.0003(1.18)0.0497 ± 0.0023 **(11.37)
DOX0.0311 ± 0.0021(1.00)1.3346 ± 0.1267(1.00)
 + 0.1 μmol/L osimertinib0.0292 ± 0.0022(1.07)0.4527 ± 0.0312 **(2.95)
 + 0.2 μmol/L osimertinib0.0307 ± 0.0018(1.01)0.2782 ± 0.0216 **(4.80)
 + 0.4 μmol/L osimertinib0.0279 ± 0.0030(1.11)0.1875 ± 0.0129 **(7.12)
 + 10 μmol/L VRP0.0294 ± 0.0035(1.06)0.1241 ± 0.0112 **(10.75)
Paclitaxel0.0021 ± 0.0005(1.00)0.4912 ± 0.0274(1.00)
 + 0.1 μmol/L osimertinib0.0020 ± 0.0006(1.05)0.1695 ± 0.0136 **(2.90)
 + 0.2 μmol/L osimertinib0.0019 ± 0.0002(1.11)0.1074 ± 0.0095 **(4.57)
 + 0.4 μmol/L osimertinib0.0017 ± 0.0008(1.24)0.0563 ± 0.0053 **(8.72)
 + 10 μmol/L VRP0.0019 ± 0.0004(1.11)0.0367 ± 0.0031 **(13.38)
Cisplatin0.6688 ± 0.0715(1.00)1.4710 ± 0.0543(1.00)
 + 0.4 μmol/L osimertinib0.6727 ± 0.0673(0.99)1.4860 ± 0.0472(0.99)
MCF-7MCF-7/adr (ABCB1)
DOX0.0917 ± 0.0031(1.00)4.3203 ± 0.2543(1.00)
 + 0.1 μmol/L osimertinib0.0923 ± 0.0027(0.99)2.3475 ± 0.1542(1.84)
 + 0.2 μmol/L osimertinib0.0861 ± 0.0048(1.07)0.7412 ± 0.0436 **(5.83)
 + 0.4 μmol/L osimertinib0.0889 ± 0.0065(1.03)0.4959 ± 0.0312 **(8.71)
 + 10 μmol/L VRP0.0934 ± 0.0076(0.98)0.2667 ± 0.0722 **(16.20)
Paclitaxel0.0089 ± 0.0009(1.00)0.6967 ± 0.0543(1.00)
 + 0.1 μmol/L osimertinib0.0087 ± 0.0008(1.02)0.2916 ± 0.0275 *(2.39)
 + 0.2 μmol/L osimertinib0.0099 ± 0.0009(0.90)0.1594 ± 0.0114 **(4.37)
 + 0.4 μmol/L osimertinib0.0083 ± 0.0007(1.07)0.0815 ± 0.0078 **(8.55)
 + 10 μmol/L VRP0.0085 ± 0.0006(1.05)0.0443 ± 0.0042 **(15.73)
Cisplatin1.0585 ± 0.2354(1.00)5.3143 ± 0.2987(1.00)
 + 0.4 μmol/L osimertinib1.0960 ± 0.2574(0.97)5.4766 ± 0.6573(0.97)
S1S1-MI-80 (ABCG2)
MX0.1293 ± 0.0982(1.00)19.5305 ± 0.7642(1.00)
 + 0.05 μmol/L osimertinib0.1187 ± 0.0875(1.09)7.5039 ± 0.5428**(2.60)
 + 0.1 μmol/L osimertinib0.1098 ± 0.0542(1.18)3.1861 ± 0.6539 **(6.13)
 + 0.2 μmol/L osimertinib0.1152 ± 0.0362(1.12)1.1542 ± 0.3214 **(16.92)
 + 2.5 μmol/L FTC0.1360 ± 0.0487(0.95)0.8689 ± 0.3573**(22.48)
Topotecan0.2677 ± 0.0125(1.00)14.4553 ± 0.8625(1.00)
 + 0.05 μmol/L osimertinib0.2549 ± 0.0265(1.05)4.5483 ± 0.6722**(3.18)
 + 0.1 μmol/L osimertinib0.2763 ± 0.0627(0.97)3.4653 ± 0.2986**(4.17)
 + 0.2 μmol/L osimertinib0.2451 ± 0.0362(1.09)1.9404 ± 0.3497**(7.05)
 + 2.5 μmol/L FTC0.2634 ± 0.0543(1.02)0.7717 ± 0.2574 **(18.73)
Cisplatin17.6519 ± 0.4527(1.00)18.4539 ± 0.7862(1.00)
 + 0.2 μmol/L osimertinib16.3288 ± 0.6793(1.08)17.6709 ± 0.8095(1.04)
H460H460/MX20 (ABCG2)
MX0.0033 ± 0.0004(1.00)0.4017 ± 0.0763(1.00)
 + 0.1 μmol/L osimertinib0.0028 ± 0.0007(1.18)0.1480 ± 0.0659**(2.71)
 + 0.2 μmol/L osimertinib0.0030 ± 0.0009(1.10)0.0903 ± 0.0864**(4.45)
 + 0.4 μmol/L osimertinib0.0027 ± 0.0008(1.22)0.0519 ± 0.0402**(7.74)
 + 2.5 μmol/L FTC0.0025 ± 0.0004(1.32)0.0397 ± 0.0675**(10.12)
Cisplatin3.1759 ± 0.7622(1.00)7.7430 ± 0.5439(1.00)
 + 1.5 μmol/L osimertinib2.9254 ± 0.5421(1.09)7.2012 ± 0.4328(1.08)
  • NOTE: MTT assay was performed to analyze the cell survival after treatment with anticancer agents in the absence or presence of osimertinib. VRP (specific inhibitor of ABCB1) and FTC (specific inhibitor of ABCG2) were used as the positive control. The fold reversal of MDR (values given in parentheses) was calculated by dividing the IC50 value for cells with the anticancer drug in the absence of osimertinib by that obtained in the presence of osimertinib. Data represent the mean ± SD of at least three independent experiments.

  • *, P < 0.05; **, P < 0.01.