Table 1

Growth inhibition induced by TM in the presence and absence of AG14361 in human colon and ovarian cancer cell lines in relation to MMR statusa

Cell lineGenotypeGI50m)b
MMRp53TMTM + AG14361PF50c
HCT + Chr3+wt319 ± 80d192 ± 40 1.5 ± 0.5 NS
HCT116wt841 ± 128225 ± 69 3.7 ± 1.2 * e
Fold resistant a 2.5 ± 0.7 * 1.0 ± 0.3 NS
A2780+wt154 ± 2362.5 ± 10 2.5 ± 0.6 *
CP70wt/mut1012 ± 153194 ± 33 5.2 ± 1.2 *
Fold resistant e 6.6 ± 1.3 * 3.1 ± 0.7 *
CP70-ch3+wt/mut609 ± 102185 ± 16 3.3 ± 0.6 *
CP70-ch2wt/mut1241 ± 93243 ± 38 5.1 ± 0.9 *
Fold resistant 2.0 ± 0.4 * 1.3 ± 0.3 NS
  • a TM, temozolomide; MMR, mismatch repair; wt, wild type; mut, mutant;

  • * , significant resistance or potentiation (P < 0.05: paired Student’s t test); NS, not significant.

  • b GI50 is the concentration of TM ± 400 nm AG14361 required to inhibit growth by 50% after 5 days of continuous exposure.

  • c PF50 is calculated as GI50 temozolomide alone ÷ GI50 temozolomide + AG14361.

  • d Data are mean ± SD of GI50 values from at least three independent experiments.

  • e Fold resistance was calculated as the ratio of the GI50 in MMR− cells ÷ GI50 in MMR+ cells.