Table 3.

Effect of the combination between the USP1/UAF1 inhibitor pimozide with the chemotherapy agent cisplatin in a panel of NSCLC cell lines

Cell line	Cisplatin	Pimozide	Ratio C:P	C.I.	Combination effect
	IC50 (μM)	IC50 (μM)
H322 (s)	1.6	11.6	1:7	1.3	Antagonistic
SKLU-1 (s)	2.4	13.7	1:6	1.2	Antagonistic
SW1573 (s)	4.4	10.5	1:2	2.0	Antagonistic
H522 (s)	5.0	10.8	1:2	0.9	Additive
H1299 (r)	7.5	7.0	1:1	0.6	Synergistic
H1703 (r)	8.8	5.0	2:1	1.0	Additive
H520 (r)	13.7	8.7	2:1	1.1	Additive

The IC₅₀ value for cisplatin and pimozide was calculated for each cell line as described in Figure 4. Cell lines were classified as “cisplatin-sensitive” (s) if their IC₅₀ for this drug was below the mean value of the panel (6.2 μM), or as “cisplatin-resistant” (r) if their IC₅₀ was above the mean. Treatment with the two drugs in combination was carried out using a constant ratio cisplatin:pimozide (Ratio C:P) that was individually established for each cell line as the ratio of the IC₅₀ values for each single drug. The combination index (C.I) value was calculated at a full range of Fa values using CalcuSyn, as described in Figure 4. We calculated the final C.I. value for each experiment as the average C.I. at Fa = 0.5, 0.75 and 0.9. At least three independent experiments per cell line were carried out, and the C.I. value indicated in the Table represents the mean of the final C.I. values of these experiments. According to the C.I., the nature of the interaction between the drugs (Combination effect) was classified as synergistic (C.I. < 0.8), additive (0.8 < C.I. < 1.2) or antagonistic (C.I. > 1.2).