Table 2

Potentiation of TM-induced growth inhibition by AG14361 and BG in human colon and ovarian cancer cell lines matched for p53 status and MGMT activitya

HCT + Chr3HCT116CP70-ch3CP70-ch2
p53wtwtwt/mutwt/mut
MMR++
MGMT (fmol/mg prot.)209 ± 71b201 ± 95778 ± 74833 ± 66
GI50 TM (μm)c402 ± 85938 ± 15692 ± 92>1500
GI50 TM (μm) + BG157 ± 59996 ± 5469 ± 7≥1394
PF 50 d 3.1 ± 1.4 e 0.95 ± 0.05 9.8 ± 0.7 e ≥1.1
GI50 TM (μm) + AG14361317 ± 80257 ± 27284 ± 48503 ± 102
PF 50 1.3 ± 0.5 3.7 ± 0.5 e 2.5 ± 0.7 e >3.2
GI50 TM (μm) + BG + AG14361124 ± 32226 ± 1461.8 ± 1.7474 ± 97
PF 50 3.5 ± 1.3 e 4.2 ± 0.4 e 11 ± 1.8 e >3.4
  • a BG, benzylguanine; MGMT, methylguanine DNA methyltransferase; wt, wild type; mut, mutant; MMR, mismatch repair; TM, temozolomide.

  • b Data are mean ± SD of values from three independent experiments.

  • c GI50 is the concentration of TM, ±10 μm BG, ±400 nm AG14361 required to inhibit cell growth by 50% after 5 days of continuous exposure.

  • d PF50 is calculated as the ratio of the GI50 for TM + AG14361 and/or BG to the GI50 for TM alone.

  • e Significant potentiation (P < 0.05: paired Student’s t test).