Table 2.
Growth inhibition of parental CCRF-CEM human leukemia cells and sub-lines with single, defined mechanisms of MTX resistance during continuous (0–120 h) exposure to MTX, 13, or 14
| Drug | EC50 (nM) | |||
|---|---|---|---|---|
| CCRF-CEM | R1a (↑ DHFR) | R2b (⇓ Uptake) | R30dmc (⇓ Glun) | |
| MTX | 12.7 ± 3.3 | 915 ± 285 | 2600 ± 100 | 13.1 ± 3.4 |
| 13 | ≈18,000 | ≥15,000 | >10,000 | >20,000 |
| 14 | ≈16,000 | >20,000 | >10,000 | ≈20,000 |
Values presented are average ± SD for n > 2 or average ± range for n = 2.
a
CCRF-CEM subline resistant to MTX solely as a result of a 20-fold increase in wild-type DHFR protein and activity.27
b
CCRF-CEM subline resistant as a result of decreased uptake of MTX.28
c
CCRF-CEM subline resistant to MTX solely as a result of decreased polyglutamylation; this cell line has 1% of the FPGS specific activity (measured with MTX as the folate substrate) of parental CCRF-CEM.29