Modulation of the Ribonucleotide Reductase-Antimetabolite Drug Interaction in Cancer Cell Lines
Table 1
ratios of clones with high and low RRM1 expression of three cell lines for different cytotoxic agents.
H23
MCF7
HCT8
Control
RRM1 up
RRM1 down
Control
RRM1 up
RRM1 down
Control
RRM1 up
RRM1 down
IC50
IC50 Ratio
IC50 Ratio
IC50
IC50 Ratio
IC50 Ratio
IC50
IC50 Ratio
IC50 Ratio
Mean
SE
Mean
SE
Mean
SE
Mean
SE
Mean
SE
Mean
SE
Antimetabolites
Gemcitabine
0.010
0.22
0.06
0.008
0.92
0.12
0.013
0.16
0.08
Hydroxyurea
686.400
0.87
0.01
1.18
0.05
0.960
1.11
0.04
0.05
1547.900
1.20
0.10
0.02
Methotrexate
0.025
0.21
0.87
0.26
0.022
1.01
0.07
1.14
0.06
0.026
1.03
0.12
1.03
0.17
Pemetrexed
0.105
0.25
0.80
0.02
0.036
0.03
1.20
0.09
0.109
0.07
0.38
5-Fluorouracil
0.911
0.97
0.05
3.183
1.27
0.26
39.223
0.50
Platinum Compounds
Cisplatin
2.692
0.06
0.02
25.161
1.13
0.02
0.80
0.04
5.653
0.04
1.04
0.11
Carboplatin
66.328
0.61
0.16
120.000
0.97
0.08
1.15
0.09
21.558
no data
no data
Mitosis Inhibitors
Docetaxel
0.003
1.21
0.44
0.90
0.17
0.001
0.89
0.12
0.79
0.12
0.013
0.94
0.16
1.18
0.04
Vinorelbine
0.034
0.96
0.16
1.00
0.21
0.010
1.02
0.10
0.98
0.14
0.072
0.98
0.10
1.14
0.14
Topoisomerase Inhibitors
Etoposide
0.227
1.15
0.06
1.14
0.06
0.291
0.89
0.10
1.06
0.11
0.183
1.18
0.14
1.03
0.17
IC50 values for the wild-type cell lines for each of the drugs tested are listed in the column labeled “Control”. The IC50 ratios for RRM1 up- and down-regulated clones for cell lines H23, MCF7, and HCT8 were calculated as described in the Material and Methods section. Values greater than 1 indicated that higher drug concentrations are required to reach the IC50; that is, drug resistance. Values smaller than 1 indicated that the lower drug concentrations are required to reach the IC50; that is, drug sensitivity. Indicates values considered to be significantly changed.
