Table 1.

Growth inhibition by antifolates

Cell lineHCT-15 (wild-type)PT1 (nontransfected)PT1-RFCPT1-Vector
Cells grown in 5-CHO-THF
    Methotrexate110 ± 11 (7)474 ± 33 (7)70 ± 7 (4)350 ± 20 (4)
    Pemetrexed410 ± 61 (7)128 ± 13 (7)382 ± 36 (4)155 ± 23 (4)
    PT6324.9 ± 1.0 (7)871 ± 122 (7)2.5 ± 0.2 (4)1,125 ± 25 (4)
    Trimetrexate510 ± 59 (7)79 ± 9 (7)305 ± 39 (4)31 ± 7 (4)
    ZD169417 ± 3 (3)360 ± 61 (3)
    AG331 (μmol/L)19 ± 1 (2)*19 ± 1 (2)*
Cells grown in folic acid
    Methotrexate44 ± 7 (6)670 ± 45 (6)19 ± 1 (3)550 ± 29 (3)
    Pemetrexed250 ± 54 (6)1,133 ± 185 (6)77 ± 15 (3)1,200 ± 58 (3)
    PT6322.7 ± 0.7 (6)860 ± 162 (6)0.9 ± 0.1 (3)783 ± 109 (3)
    Trimetrexate112 ± 19 (6)*81 ± 10 (6)*48 ± 7 (3)*97 ± 29 (3)*
  • NOTE: HCT-15 wild-type cells, PT1 cells, and PT1 cells transfected with either wild-type RFC or empty vector were grown for at least a week with the folate growth sources indicated, then exposed to a spectrum of concentrations of different antifolates for a period of 6 days. The IC50s are the average ± SE and are expressed in nmol/L, except for AG331. The number of experiments is indicated in parentheses. All differences between HCT-15 and PT1 cells and between PT1-RFC and PT1-Vector cells are statistically significant (P < 0.01) except for the values marked with an asterisk (*, P > 0.1).