TABLE 2

Effect of vandetanib and PYR on the cytotoxicity of cisplatin when added to variously transfected HEK293 cells

HEK293 cells stably transfected with transporter (or vector only) were treated with various concentrations of cisplatin in the presence or absence of vandetanib or PYR. After 3 days, cells were counted and IC₅₀₍_CN₎ values were generated (see Materials and Methods). Data are reported as the mean ± S.D. (n = 4 determinations).

Drug	Mock-HEK	OCT2-HEK		MATE1-HEK		MATE2K-HEK
Drug	IC₅₀₍_CN₎	IC₅₀₍_CN₎	RF^a	IC₅₀₍_CN₎	RF^a	IC₅₀₍_CN₎	RF^a
Cisplatin only	2.34 ± 0.31	1.36 ± 0.19	1.7	1.12 ± 0.13	2.1	0.85 ± 0.09^b	2.8
Cisplatin + vandetanib (2.5 µM)	2.31 ± 0.31	1.47 ± 0.24	1.6	2.39 ± 0.44^c	1.0	1.99 ± 0.16^c	1.2
Cisplatin + PYR (2.5 µM)	ND	ND	–	2.28 ± 0.19	1.1	2.23 ± 0.28^c	1.1
Cisplatin + PYR (50 µM)	2.39 ± 0.42	2.38 ± 0.31	1.0	ND	–	ND	–

↵ND, not determined; RF, resistance factor.^aIC₅₀₍_CN₎ after addition of cisplatin to HEK293 cells stably transfected with transporter versus the IC₅₀₍_CN₎ after addition of cisplatin to vector only (mock) transfected HEK293 cells; PYR, pyrimethamine.
↵b Statistically significant left shift in IC₅₀₍_CN₎ versus cisplatin alone in mock-HEK cells (P < 0.05).
↵c For MATE1-HEK and MATE2K-HEK cells, there was a statistically significant right shift in IC₅₀₍_CN₎ versus cisplatin alone in MATE1-HEK and MATE2K-HEK (P < 0.05).