Treatment with the PARP inhibitor, niraparib, sensitizes colorectal cancer cell lines to irinotecan regardless of MSI/MSS status

Table 1 Niraparib potentiates the effects of SN-38 in MSI and MSS cell lines

		7 day EC50 (nM)		Combination EC50 (shift of SN-38 EC50 in presence of Niraparib)
				Niraparib
	Cell line	Niraparib	SN-38	125 nM	250 nM	1000 nM
MSI	DLD1	3560	3.63	0.992	1.67	1.68
	HCT8	2130	3.60	2.07	1.54	1.35
	HCT15	1685	3.77	3.47	3.44	1.73
	HCT116	6915	0.180	0.125	0.155	0.0991
	LOVO	2010	3.43	2.3	3.53	2.4
	LS174T	1310	0.331	0.257	0.208	0.231
	LS180	3730	0.474	0.399	0.395	0.389
	LS411N	1875	3.57	1.21	1.11	0.729
	RKO	1870	0.958	0.593	0.778	0.184
	RKOE6	1270	0.730	0.426	0.422	0.464
	SNUC2A	>10000	3.23	3.04	2.72	2.52
	SW48	>10000	1.79	0.886	0.762	0.598
MSS	COLO205	1990	1.57	0.572	0.475	0.531
	HT29	6880	4.29	3.07	3.64	1.75
	NCI-H-508	>10000	3.63	1.70	3.31	1.41
	SK-CO-1	1090	0.416	0.178	0.334	0.143
	SW403	>10000	3.39	1.14	1.87	0.387
	SW480	>10000	29.0	11.9	11.6	8.7
	SW620	552	5.91	3.62	UR	UR
	SW837	>10000	UR	UR	UR	UR
	SW948	7195	6.67	3.85	4.47	2.80
	SW1116	>10000	UR	UR	UR	UR
	SW1417	>10000	27.7	29.2	28.3	31.0
	SW1463	>10000	26.4	22.2	UR	UR
	T84	1460	1.01	0.491	0.352	0.210

7 day EC50 data for niraparib alone, SN-38 alone, and the combination EC50 at 125, 250 and 1000 nM of niraparib in a panel of 25 MSI and MSS CRC cell lines . The niraparib EC50 values are the average of n = 2 from previous experiments. The SN-38 EC50 values reported are for n = 1 for the experiment done on that day. Values listed under 125, 250, and 1000nM niraparib are the EC50 values for SN-38 in the presence of 125, 250 or 1000 nM niraparib (combination EC50). EC50 data was calculated using the inflection point of the curve in a 4 parameter fit in SoftMax Pro 5.2. UR indicates that the data is unreportable due to an inadequate curve.