Figure 4. Effects of tivozanib on the efflux of [³H]-paclitaxel and [³H]-mitoxantrone.

(A) Tivozanib decreases the efflux of [³H]-paclitaxel in HEK293/pcDNA3.1 cells and the transfected cell line HEK/ABCB1. (B) Tivozanib decreases the efflux of [³H]-mitoxantrone in HEK293/pcDNA3.1 cells and the transfected cell line ABCG2-482-R2. After pretreating cells with or without tivozanib 5 μM for 2 h, cells were incubated with 0.1 μM [³H]-paclitaxel or 0.1 μM [³H]-mitoxantrone for another 2 h at 37°C. After being rinsed three times with cold phosphate-buffered saline, cells were incubated with or without reversal agents in a fresh medium at 37°C. After 0, 30, 60 or 120 min, the same numbers of cells (1 × 10⁶) were removed and washed three times with ice-cold phosphate-buffered saline. The cells were then lysed and placed in scintillation fluid in order to measure their radioactivity. The data points represent the mean ± standard deviation of triplicate determinations. Experiments were performed at least three times independently. *p < 0.05 for values versus those in the control group for (A) HEK/ABCB1 plus tivozanib (5 μM) and (B) ABCG2-482-R2 plus tivozanib (5 μM).

FTC: Fumitremorgin C.