The radiosensitising effect of gemcitabine and its main metabolite dFdU under low oxygen conditions is in vitro not dependent on functional HIF-1 protein

Table 2 Radiobiological parameters for the combination of gemcitabine or dFdU with irradiation under normoxia or hypoxia

Condition	OER	SD	DEF	SD	CI	SD		ID₅₀	SD		MID	SD		SF₂	SD		% survival	SD
MDA-MB-231 wt
24 N → RT								2.83	1.03		3.30	1.06		65.61	21.99		100	0
24 N + 8 nM dFdC → RT			1.70	0.96	0.865	0.175	*	1.70	0.72	††	2.00	0.76	††	37.48	17.47	††	60	27	††
24 N + 2 μM dFdU → RT			2.18	0.57	0.701	0.214	*	1.46	0.22	††	1.62	0.28	††	29.63	9.83	††	41	12	††
24 H → RT	1.43	0.61						3.67	1.03		4.14	0.98		72.96	16.96		93	11
24 H + 8 nM dFdC → RT			1.59	0.46	0.683	0.243	¶	2.37	1.32	††	2.51	1.02	††	58.92	17.91		60	25	††
24 H + 2 μM dFdU → RT			2.34	0.71	0.687	0.285	¶	1.87	0.59	††	2.34	0.32	†,††	49.39	15.89		44	8	††
MDA-MB-231 EV
24 N → RT								2.35	1.29		2.65	1.37		53.68	34.97		100	0
24 N + 8 nM dFdC → RT			1.70	0.82	0.932	0.273		1.59	0.66		1.61	0.24		28.02	8.46		39	9	††
24 N + 2 μM dFdU → RT			1.74	1.06	0.839	0.231	*	1.80	0.75		2.05	0.72		40.16	26.53		45	23	††
24 H → RT	1.57	0.76						3.41	1.78		4.42	1.81		68.53	32.22		92	36
24 H + 8 nM dFdC → RT			1.77	0.85	0.381	0.023	¶	2.00	0.47		2.56	1.04		52.56	22.09		40	30	††
24 H + 2 μM dFdU → RT			2.35	1.16	0.711	0.245	*	2.01	0.45		2.59	0.71		48.64	7.71		49	24
MDA-MB-231 dnHIF
24 N → RT								3.02	1.42		3.46	1.73		69.79	38.04		100	0
24 N + 8 nM dFdC → RT			1.50	0.75	0.761	0.182	*	1.82	1.18		2.25	1.16		42.90	26.39		30	15	††
24 N + 2 μM dFdU → RT			2.45	0.67	0.818	0.274	*	1.86	0.99		2.07	1.13		45.32	33.00		61	15	††
24 H → RT	1.43	0.54						3.80	1.40		4.93	1.47		81.34	35.51		97	19
24 H + 8 nM dFdC → RT			2.04	0.93	0.587	0.280	¶	1.90	0.86	††	1.97	0.69	††	42.62	20.43	††	32	15	††
24 H + 2 μM dFdU → RT			2.08	0.52	0.798	0.311	*	2.54	0.77		2.85	0.83	††	59.16	14.76		63	16	††

dFdC: gemcitabine; RT: irradiation; N: normoxia; H: hypoxia; SD: standard deviation; OER: oxygen enhancement ratio; DEF: dose enhancement factor; CI: combination index, ID₅₀: radiation dose producing a surviving fraction of 50%; MID: mean inactivation dose (MID), SF₂: surviving fraction at 2 Gy; % survival: representing the cytotoxic effect of gemcitabine (dFdC) or dFdU and/or hypoxia alone, 0 Gy.
†: p < 0.05 vs. corresponding normoxic condition (same treatment, same cell line); ††: p < 0.05 vs. corresponding untreated condition (same pO₂, same cell line).
*: moderate synergism (0.7 > CI > 0.9); ¶: synergism (CI < 0.7).
All results are from at least 3 independent experiments ± SD.

ISSN: 1471-2407