Fig. 6

The effect of the VEGF/PI3K/AKT signaling pathway on the proangiogenic effect of CDDP. A Schematic representation of the experimental design. Twenty-four hpf Tg(fli1:EGFP) embryos were pretreated with various concentrations of the PI3K inhibitor LY294002 (LY, 0.3–3 µM) and the AKT inhibitor VIII (AKTi, 0.03–0.3 µM) for 30 min and were then cotreated with VRI (100 nM) and CDDP (1.2 mg/mL) for 24 h. Ten consecutive ISVs in the framed area were observed in each embryo. Fifteen embryos were analyzed in each group, and the experiment was replicated four times. B CDDP relieved the abnormal development of ISVs, which could be inhibited by 3 µM LY, 0.1 or 0.3 µM AKTi. C Twenty-four hpf embryos were treated with various concentrations of LY (0.3–3 µM) and AKTi (0.03–0.3 µM) for 24 h. Both inhibitors could promote angiogenesis of ISVs at specific concentrations. D The angiogenic efficacy of CDDP could be weakened by LY or AKTi at specific concentrations. The ISV index of each zebrafish embryo was calculated as (the number of intact vessels × 1) + (the number of defective vessels × 0.5). Data are presented as the mean ± SEM