Table 1. Interaction of selected kinases with RRM1-dependent gemcitabine efficacy.

IC50 ratio*	BLK	CHK1	KDR	KIT	MET	TEC	IC50 in siRNAControl [nM]
H23(control)	1.20	0.55	0.82	0.96	1.13	0.64	6.99
H23-R1(RRM1 high)	1.10	0.26	1.39	0.84	1.19	0.74	11.73
H23-shR1(RRM1 low)	1.39	3.80	1.26	0.99	1.17	1.24	4.68
MCF7(control)		0.45				0.68	3.06
MCF7-R1(RRM1 high)		0.18				0.67	58.58
MCF7-shR1(RRM1 low)		1.40				0.72	1.09
H125		0.76				0.94	8.20×103
H650		0.02				0.95	47.12×103
H1648		0.49				0.91	10.11×103
H2122		0.29				1.00	54.54×103
H23-G-C8		0.28					40.67
H23-G-C23		0.31					41.95
H1299-G-C2		0.28					243.07
H1299-G-C18		0.28					248.06

^*The IC50 ratio was calculated by dividing the siRNA-specific IC50 by the control IC50. Cell lines H23, MCF7, and H1299 were exposed to gemcitabine for four 4 days. H125, H650, H1648, and H2122 were exposed for 5 to 7 days (a 4-day exposure yields IC50 values above 1 mM). RRM1 knockdown in the gemcitabine resistant clones restored sensitivity (IC50 ratios: 0.15 for H23-G-C8 and H23-G-C23, 0.19 for H1299-G-C2 and 0.09 for H1299-G-C18).