Figure 2. Effect of moteanib on the accumulation and efflux of [³H]-paclitaxel.

(A) The accumulation of [³H]-paclitaxel was measured after the cells (parental KB-3-1 and ABCB1 overexpressing KB-C2 drug selected cell line) were pre-incubated with or without motesanib or verapamil for 2 h at 37°C and then incubated with 0.01 µM [³H]-paclitaxel for another 2 h at 37°C. Columns are the mean of triplicate determinations; error bars represent SD. (B) The effect of motesanib on the efflux of [³H]-paclitaxel from KB-3-1 and KB-C2 cells. Cells were pre-treated with or without motesanib or verapamil at 3 µM for 2 h at 37°C and further incubated with 0.01 µM [³H]-paclitaxel at 37°C for 2 h. Cells were then incubated in the fresh medium with or without the reversal agents for different time periods at 37°C. Cells were then collected and the intracellular levels of [³H]-paclitaxel were determined by scintillation counting. A time course versus percentage of intracellular [³H]-paclitaxel remaining (%) was plotted (0, 30, 60, 120 min). Lines are the mean of triplicate determinations; error bars represent SD. * indicates P < 0.05, ** indicates P<0.01 versus the control group. The above figures are from three independent experiments, each done in triplicate.