TABLE 1.

Effects of neratinib in reversing ABCB1-, ABCG2-, and ABCC1-mediated drug resistance

Cell survival rates were determined with MTT assays, as described under Materials and Methods. Data are the mean ± S.D. of at least three independent experiments performed in triplicate. The fold reversal of MDR was calculated by dividing the IC₅₀ for cells with the anticancer agent in the absence of neratinib, VRP, or fumitremorgin C by that in the presence of neratinib, VRP, or fumitremorgin C.

Compounds	IC50 (Reversal)
	KB	KBv200 (ABCB1)	MCF-7	MCF-7Adr (ABCB1)	MCF-7/FLV1000 (ABCG2)	HL60	HL60/Adr (ABCC1)
	μM (fold)
Doxorubicin	0.031 ± 0.006 (1.00)	7.122 ± 0.430 (1.00)
+ 0.25 μM Neratinib	0.025 ± 0.004 (1.26)	2.135 ± 0.103 (3.34)*
+ 0.5 μM Neratinib	0.018 ± 0.003 (1.69)*	1.550 ± 0.278 (4.60)**
+ 1.0 μM Neratinib	0.014 ± 0.003 (2.20)*	0.588 ± 0.207 (12.11)**
+ 10 μM Verapamil	0.029 ± 0.004 (0.94)	0.250 ± 0.070 (28.45)**
Vincristine	0.0025 ± 0.0002 (1.00)	1.440 ± 0.130 (1.00)
+ 0.25 μM Neratinib	0.0025 ± 0.0004 (1.00)	0.765 ± 0.070 (1.88)**
+ 0.5 μM Neratinib	0.0025 ± 0.0003 (1.00)	0.269 ± 0.028 (5.36)**
+ 1.0 μM Neratinib	0.0021 ± 0.0003 (1.16)	0.035 ± 0.002 (41.17)**
+ 10 μM Verapamil	0.0023 ± 0.0004 (1.06)	0.018 ± 0.001 (82.48)**
Paclitaxel	0.0016 ± 0.0002 (1.00)	0.222 ± 0.021 (1.00)
+ 0.25 μM Neratinib	0.0016 ± 0.0002 (1.00)	0.074 ± 0.009 (2.99)**
+ 0.5 μM Neratinib	0.0015 ± 0.0001 (1.07)	0.022 ± 0.004 (10.13)**
+ 1.0 μM Neratinib	0.0017 ± 0.0002 (0.94)	0.005 ± 0.001 (43.34)**
+ 10 μM Verapamil	0.0016 ± 0.0003 (1.00)	0.004 ± 0.001 (50.76)**
Cisplatin	3.022 ± 0.30 (1.00)	3.951 ± 0.40 (1.00)
+ 1.0 μM Neratinib	2.888 ± 0.28 (1.05)	3.354 ± 0.34 (0.97)
+ 10 μM Verapamil	2.943 ± 0.30 (1.03)	4.071 ± 0.40 (1.18)
Doxorubicin			0.283 ± 0.02 (1.00)	11.675 ± 1.186 (1.00)
+ 0.25 μM Neratinib			0.262 ± 0.03 (1.08)	2.413 ± 0.196 (4.84)**
+ 0.5 μM Neratinib			0.215 ± 0.02 (1.31)*	1.443 ± 0.27 (8.09)**
+ 1.0 μM Neratinib			0.163 ± 0.01 (1.74)*	0.944 ± 0.06 (12.37)**
+ 10 μM Verapamil			0.285 ± 0.03 (0.99)	0.478 ± 0.076 (24.40)**
Mitoxantrone			0.115 ± 0.012 (1.00)		6.723 ± 0.632 (1.00)
+ 0.125 μM Neratinib			0.109 ± 0.011 (1.05)		6.231 ± 0.611 (1.07)
+ 0.25 μM Neratinib			0.107 ± 0.011 (1.07)		6.081 ± 0.602 (1.11)
+ 0.5 μM Neratinib			0.114 ± 0.010 (1.02)		5.149 ± 0.521 (1.31)
+ 2.5 μM Fumitremorgin C			0.109 ± 0.011 (1.06)		0.276 ± 0.021 (24.36)**
Doxorubicin						0.074 ± 0.007 (1.00)	3.622 ± 0.313 (1.00)
+ 0.125 μM Neratinib						0.078 ± 0.008 (0.95)	3.668 ± 0.367 (1.12)
+ 0.25 μM Neratinib						0.069 ± 0.006 (1.08)	3.600 ± 0.360 (1.14)
+ 0.5 μM Neratinib						0.061 ± 0.006 (1.21)	3.083 ± 0.301 (1.18)
+ 40 μM MK571						0.065 ± 0.006 (1.13)	0.0825 ± 0.008 (5.50)**

^*P < 0.05 versus the values obtained in the absence of neratinib, VRP, or fumitremorgin C.

^**P < 0.01 versus the values obtained in the absence of neratinib, VRP, or fumitremorgin C.