Table 4.

Effect of FTC analogues on P-gp- and MRP1-mediated drug resistance

Shown are the effective concentrations of inhibitor compounds for reversal of 50% (EC50) or 90% (EC90) of the resistance of the cell line for the drug specified. Values shown are means ± SD of quadruplicate repeats; 95% confidence intervals may be obtained by multiplying the SDs by 1.84. Independent repetition of the experiments gave similar results, not differing by >15% from the means shown.

Ko132Ko134Ko143GF120918BSOa
P-gp-mediated paclitaxel resistanceb
 EC50m)2.3 ± 0.40.61 ± 0.071.0 ± 0.30.0030 ± 0.0004ND
 EC90m)5.0 ± 0.42.8 ± 0.45.5 ± 0.50.0045 ± 0.0004ND
MRP1-mediated etoposide resistancec
 EC50m)1.6 ± 0.41.8 ± 0.52.0 ± 0.4ND0.65 ± 0.15
 EC90m)>8>8>8ND>8
  • a l-Buthionine sulfoximine depletes glutathione and is thus an indirect inhibitor of MRP1. ND, not determined.

  • b Assessed in MDR1-transduced 77.1 cells (see “Materials and Methods” and Table 3 for properties): IC50 for paclitaxel = 2.4 ± 0.2 μm (n = 3), RF = 200, compared with the parent 77.1 cell line.

  • c Assessed in MRP1-transfected 2008 cells (see “Materials and Methods” and Table 3 for properties): IC50 for etoposide = 5.2 ± 0.4 μm (n = 4), RF = 22 compared with the parent 2008 cell line.