Modulation of the Ribonucleotide Reductase-Antimetabolite Drug Interaction in Cancer Cell Lines
Table 3
Endogenous RRM1 levels and gemcitabine, pemetrexed, and carboplatin efficacy in 26 NSCLC cell lines.
Cell Line
ATCC #
Histological Subtype
p53 mutation () based on CCDS11118.1 cod on 72 either proline or arginine
K-ras mutation
Doubling Time (hr)
RRM1
RRM2a
RRM2b
ERCC1
TS
TP53
P38
MCM2
Gem IC50 (uM)
Pem IC50 (uM)
Carbo IC50 (uM)
A549
CLL-185
AD-BAC
wt
G12S
48
2.30
1.08
1.23
2.49
0.90
0.53
0.91
0.83
0.010
0.103
41.003
ADLC5M2
—
AD
wt
wt
24
2.42
1.79
0.30
2.40
0.66
0.12
0.58
1.22
0.079
0.044
6.678
EPLC65H
—
SQ
wt
wt
47
2.83
1.07
0.55
3.92
1.23
0.12
1.22
0.97
0.019
0.039
7.590
H125
CRL-5801
AD/SQ
wt
70
1.65
2.53
1.05
3.64
0.60
0.00
0.92
0.87
1000
0.374
39.678
H1299
CRL-5803
NSCLC-NOS
homozygous deletion
wt
46
1.92
2.43
2.18
1.31
0.91
0.00
2.01
1.37
0.024
0.236
27.273
H1355
CRL-5865
AD
E258K
G13C
36
2.04
2.32
1.08
3.68
1.12
0.58
0.54
0.94
0.006
0.355
30.651
H157
CRL-5802
SQ
G12R
58
2.22
2.80
1.16
0.73
0.73
0.03
1.65
1.01
0.036
0.433
21.766
H1648
CRL-5882
AD
frame shift codon 35;
wt
57
2.26
1.14
1.32
0.27
0.08
0.00
1.55
1.58
1000
1000
19.730
H1650
CRL-5883
AD
wt
wt
49
0.83
1.58
1.07
1.09
0.08
0.02
0.97
0.81
0.020
0.053
14.535
H1703
CRL-5889
AD
wt
wt
42
0.91
2.45
1.45
0.73
0.66
0.04
0.64
1.02
0.002
0.173
28.421
H1975
CRL-5908
AD
R273H
wt
39
1.94
2.24
1.05
0.13
0.15
1.01
1.25
1.05
0.145
0.051
19.250
H2122
CRL-5985
AD
Q16L; C176F
G12C
72
1.04
1.42
0.61
0.90
0.05
0.37
0.95
0.92
1000
0.054
56.217
H2172
CRL-5930
NSCLC-NOS
frame shift codon 72;
wt
45
1.99
0.29
2.20
1.21
0.00
0.00
0.94
1.00
0.435
0.533
10.800
H2228
CRL-5935
AD
wt
50
0.68
0.12
0.25
1.53
0.09
0.55
0.63
1.18
0.023
0.039
11.036
H226
CRL-5826
SQ
wt
wt
76
2.30
0.45
3.28
0.79
0.24
0.45
1.63
0.96
7.491
1000
37.317
H23
CRL-5800
AD
M246I
G12C
45
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
0.008
0.125
21.220
H292
CRL-1848
ME
wt
wt
31
2.11
1.90
1.13
2.08
0.93
0.61
1.26
0.73
0.011
0.026
30.326
H322
CRL-5806
AD-BAC
R248L
wt
36
1.26
1.65
1.06
1.65
0.38
0.72
0.76
1.02
0.016
0.118
41.434
H358
CRL-5807
AD-BAC
homozygous deletion
G12C
74
1.61
1.36
1.22
3.80
0.29
0.00
2.02
1.20
0.135
0.030
23.634
H441
HTB-174
AD
R158L
G12V
58
1.86
1.91
4.49
0.99
0.05
0.47
2.77
1.87
0.033
0.093
23.545
H460
HTB-177
LC
wt
Q61H
35
2.47
2.13
1.30
1.15
0.84
0.76
0.79
0.94
0.053
0.183
85.373
H522
CRL-5810
AD
frame shift codon 191 with deletion of P
wt
108
1.08
3.17
0.73
7.04
1.10
0.22
1.74
0.89
1000
1000
21.298
H596
HTB-178
AD/SQ
G245C
wt
49
1.61
1.98
1.00
3.00
0.53
0.68
1.25
0.93
0.031
0.012
28.626
H650
CRL-5835
AD
K164N
wt
83
1.25
1.34
1.57
1.55
0.13
0.66
0.77
0.91
1000
1000
32.422
H661
HTB-183
LC
R158L; S215I
wt
47
1.34
1.05
0.86
2.06
0.88
0.54
0.88
1.23
0.024
1000
57.253
H820
HTB-181
AD
T284P
wt
68
—
—
—
—
—
—
—
—
6.883
1000
32.116
AD: adenocarcinoma, AD-BAC: adenocarcinoma with bronchoalveolar features, LC: large cell carcinoma, SQ: squamous cell carcinoma, ME: mucoepidermoid bronchial gland carcinoma, AD/SQ: mixed adenosquamous cell carcinoma, NSCLC-NOS: nonsmall cell lung cancer, not otherwise specified. IC50 values are the means of at least three experiments; 3–6 wells per experiment and dose level; 4,000 cells per well; 96 hr exposure.
