Table 1

Growth inhibition of MRP (over)expressing cells by antifolates

AntifolateIncubation time (h)2008 cells2008/MRP1 cells2008/MRP2 cells
IC50a (nm)IC50aRFbIC50aRFb
MTX7213.8 ± 5.1 nm25.7 ± 10.6 nm1.915.2 ± 4.1 nm1.1
GW18431.1 ± 0.2 nm4.0 ± 0.3c nm3.61.4 ± 0.2 nm1.3
ZD16941.1 ± 0.2 nm2.9 ± 0.9 nm2.61.8 ± 0.2 nm1.6
Trimetrexate12.2 ± 3.6 nm4.9 ± 1.4 nm0.46.0 ± 2.1 nm0.5
MTX412.9 ± 6.8 μm>1000c μm>77.5276.0 ± 82.0c μm21.4
MTX + probenecidd3.2 ± 1.1 μm7.3 ± 3.1 μm2.33.6 ± 1.2 μm1.1
MTX + probenecide1.2 ± 0.5 μm3.5 ± 1.4 μm2.91.2 ± 0.6 μm1.0
GW18431.6 ± 1.0 μm>250c μm>156.0162.0 ± 32.0c μm101.0
ZD16940.043 ± 0.011 μm0.138 ± 0.076c μm3.20.090 ± 0.066 μm2.1
ZD169410.778 ± 0.326 μm107 ± 51c μm138.03.04 ± 1.24c μm3.9
  • a IC50s are means ± SD of four to six experiments.

  • b RF, resistance factor, relative to 2008 cells.

  • c Significantly different from parental: P < 0.05.

  • d Probenecid (0.5 mm) present during 4-h drug exposure.

  • e Probenecid (0.5 mm) present during 4-h drug exposure and during the drug-free period.