Better to be alone than in bad company: The antagonistic effect of cisplatin and crizotinib combination therapy in non-small cell lung cancer

Table 1 Cell line properties and drug sensitivity

	HCC827	H1975	EBC-1	LUDLU
Properties
Histology	Adeno	Adeno	Squamous	Squamous
EGFR-status	Exon 19 deletion	L858R + T790M	Wild-type	Wild-type
cMET-status	Wild-type	Wild-type	Amplification	Wild-type
Drug sensitivity (µmol/L, IC50± SEM)
Cisplatin	8.39 ± 0.36	6.10 ± 0.07	16.52 ± 0.89	3.37 ± 0.19
Crizotinib	6.05 ± 0.11	4.00 ± 0.06	0.054 ± 0.002	8.12 ± 0.28

Cells were treated with cisplatin or crizotinib during 72 h. Drug sensitivity is given in µmol/L and given as IC₅₀± SEM of 3 separate experiments. EGFR: Epidermal growth factor receptor.

Table 2 Combination indexes for the different non-small cell lung cancer cell lines for the 3 treatment schemes

Drug scheme	HCC827		H1975		EBC-1		LUDLU-1
	Criz	CI ± SEM	Criz	CI ± SEM	Criz	CI ± SEM	Criz	CI ± SEM
Cisplatin + Crizotinib	3 μmol/L	1.58 ± 0.10	3 μmol/L	1.94 ± 0.27	0.025 μmol/L	2.08 ± 0.49	3 μmol/L	2.65 ± 0.30
	5 μmol/L	1.54 ± 0.15	5 μmol/L	1.93 ± 0.19	0.05 μmol/L	1.42 ± 0.06	4 μmol/L	2.71 ± 0.14
Cisplatin → Crizotinib	3 μmol/L	1.74 ± 0.17	3 μmol/L	1.75 ± 0.30	0.025 μmol/L	2.29 ± 0.53	3 μmol/L	1.27 ± 0.13
	5 μmol/L	2.06 ± 0.30	5 μmol/L	1.96 ± 0.14	0.05 μmol/L	2.38 ± 0.56	4 μmol/L	1.34 ± 0.15
Crizotinib → Cisplatin	1 μmol/L	2.70 ± 0.37	1 μmol/L	1.58 ± 0.24	0.025 μmol/L	2.08 ± 0.49	2 μmol/L	1.74 ± 0.14
	2 μmol/L	2.42 ± 0.21	2 μmol/L	0.95 ± 0.03	0.05 μmol/L	1.42 ± 0.06	3 μmol/L	1.89 ± 0.17

Cells were treated with the indicated fixed concentration of crizotinib (IC₂₀ and IC₄₀) either simultaneously for 72 h (indicated by “+”), or sequential with 72 h cisplatin preceding 72 h crizotinib or crizotinib preceding cisplatin (indicated by “→”). The simultaneous treatment of LUDLU-1 was performed 2 times, all other conditions were tested at least 3 times. Criz: Crizotinib; CI: Combination index; SEM: Standard error of mean.