. Author manuscript; available in PMC: 2015 Aug 15.

Published in final edited form as: Biochem Pharmacol. 2014 Jun 14;90(4):367–378. doi: 10.1016/j.bcp.2014.06.006

Table 1.

Motesanib reverses the ABCB1-mediated drug resistance to paclitaxel, colchicine and vincristine.

Treatment	KB-3-1		KB-C2

	IC₅₀ ± SD^a (µM)	RF^b	IC₅₀ ± SD(µM)	RF

Paclitaxel	0.0025 ± 0.0002	[1.0]	0.650 ± 0.039	[260.0]
+Motesanib (1 µM)	0.0026 ± 0.0001	[1.0]	0.123 ± 0.027^*	[49.2]
+Motesanib (3 µM)	0.0027 ± 0.0001	[1.1]	0.020 ± 0.007^*	[8.0]
+Verapamil (3 µM)	0.0025 ± 0.0002	[1.0]	0.017 ± 0.006^*	[6.8]
Colchicine	0.0064 ± 0.0005	[1.0]	1.519 ± 0.043	[237.3]
+Motesanib (1 µM)	0.0061 ± 0.0006	[1.0]	0.272 ± 0.037^*	[42.5]
+Motesanib (3 µM)	0.0059 ± 0.0006	[0.9]	0.120 ± 0.018^*	[18.7]
+Verapamil (3 µM)	0.0058 ± 0.0008	[0.9]	0.090 ± 0.008^*	[14.1]
Vincristine	0.0054 ± 0.0014	[1.0]	0.717 ± 0.019	[132.8]
+Motesanib (1 µM)	0.0054 ± 0.0008	[1.0]	0.083 ± 0.007^*	[15.4]
+Motesanib (3 µM)	0.0044 ± 0.0005	[0.8]	0.021 ± 0.002^*	[3.9]
+Verapamil (3 µM)	0.0033 ± 0.0013	[0.6]	0.020 ± 0.003^*	[3.7]
Cisplatin	2.467 ± 0.079	[1.0]	2.363 ± 0.109	[1.0]
+Motesanib (3 µM)	2.710 ± 0.169	[1.1]	2.551 ± 0.186	[1.0]
+Verapamil (3 µM)	2.327 ± 0.070	[0.9]	2.724 ± 0.208	[1.1]

Treatment	LLC-PK1		LLC-MDR1-WT

	IC₅₀ ± SD^a (µM)	RF^b	IC₅₀ ± SD(µM)	RF

Paclitaxel	0.025 ± 0.002	[1.0]	1.028 ± 0.070	[41.1]
+Motesanib (1 µM)	0.025 ± 0.001	[1.0]	0.182 ± 0.018^*	[7.3]
+Motesanib (3 µM)	0.023 ± 0.001	[0.9]	0.039 ± 0.003^*	[1.6]
+Verapamil (3 µM)	0.024 ± 0.001	[1.0]	0.036 ± 0.003^*	[1.4]
Cisplatin	1.919 ± 0.118	[1.0]	1.923 ± 0.113	[1.0]
+Motesanib (3 µM)	1.919 ± 0.116	[1.0]	1.924 ± 0.125	[1.0]
+Verapamil (3 µM)	1.854 ± 0.125	[1.0]	1.835 ± 0.078	[1.0]

IC₅₀ values are represented as mean ± SD of at least three independent experiments performed in triplicate.

Values represent the resistance fold (RF) obtained by dividing IC₅₀ value of antineoplastic drugs in KB-3-1 and KB-C2 cells with or without reversal agent divided by the IC₅₀ value of respective antineoplastic drug in KB-3-1 cells without reversal agent. The RF for LLC-PK1 and LLC-MDR1-WT cells was obtained in the similar manner. Cell survival assay was determined by the MTT assay as described in Section 2. Verapamil was used as a positive control of ABCB1 inhibitor.

P < 0.01 versus the control group without reversal agent.