Table 1.

Antifolate growth inhibition in parental CCRF-CEM cells and their PT523-resistant sublines


Antifolate

WT

PTR0.003

PTR0.05

PTR0.5
PT523   0.43 ± 0.19   3.7 ± 2 (8.7)   91.7 ± 15.1 (216)   1471 ± 251 (3461)  
MTX   0.86 ± 0.5   9.7 ± 5.8 (11.3)   28.1 ± 16.1 (33)   512 ± 153 (593)  
GW1843   0.5 ± 0.1   2.1 ± 0.4 (4.1)   26.5 ± 5.3 (53)   440 ± 167 (881)  
Pemetrexed (MTA)   8.1 ± 3.1   24.1 ± 0.6 (3)   208 ± 34.2 (25)   1063 ± 264 (131)  
Lometrexol (DDATHF)   13.5 ± 6.9   31.6 ± 8.9 (2.3)   595 ± 126 (44)   6945 ± 1362 (514)  
ZD9331   17.6 ± 4.6   62 ± 3.9 (3.5)   874 ± 101 (50)   4557 ± 984 (259)  
TMQ
 
15.4 ± 6.1
 
3.2 ± 1.4 (0.21)
 
2.7 ± 0.5 (0.17)
 
1.7 ± 0.4 (0.11)
 

Antifolate

WT

PTR0.003

PTR0.05

PTR0.5
PT523   0.43 ± 0.19   3.7 ± 2 (8.7)   91.7 ± 15.1 (216)   1471 ± 251 (3461)  
MTX   0.86 ± 0.5   9.7 ± 5.8 (11.3)   28.1 ± 16.1 (33)   512 ± 153 (593)  
GW1843   0.5 ± 0.1   2.1 ± 0.4 (4.1)   26.5 ± 5.3 (53)   440 ± 167 (881)  
Pemetrexed (MTA)   8.1 ± 3.1   24.1 ± 0.6 (3)   208 ± 34.2 (25)   1063 ± 264 (131)  
Lometrexol (DDATHF)   13.5 ± 6.9   31.6 ± 8.9 (2.3)   595 ± 126 (44)   6945 ± 1362 (514)  
ZD9331   17.6 ± 4.6   62 ± 3.9 (3.5)   874 ± 101 (50)   4557 ± 984 (259)  
TMQ
 
15.4 ± 6.1
 
3.2 ± 1.4 (0.21)
 
2.7 ± 0.5 (0.17)
 
1.7 ± 0.4 (0.11)
 

Values represent IC50, the drug concentration that inhibits cell growth by 50% following a 72-hour antifolate drug exposure. Results depicted are the mean (nM) ± SEM of 3 experiments.

Values in parentheses represent fold of antifolate resistance relative to parental cells.

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