Optimization of 5-FU dosing in zebrafish. (A) The internal concentration of 5-FU in embryos engrafted with SGC7901 cells was increased significantly after treatment with 5-FU (5 mM) in embryo medium, and the average internal concentration of 5-FU was 0.47, 0.49, and 0.71 ng per embryo on 1, 2, and 3 dpt, respectively (*P < 0.05). (B) Treatment for the embryos without xenograft showed that the internal concentration of 5-FU in embryos increased remarkably in both groups (P < 0.05), but the internal concentration was lower than that in embryo mediums and in the embryo rinse, indicating 5-FU enriched in embryos was a tiny fraction of administration [G#1 (group #1), daily refreshment of drug-containing medium; G#2 (group #2), continuous drug-containing medium without refreshment]. (C) zCDX study with SGC7901 cells showed that the internal concentration of 5-FU did not show difference between these two groups on each dpt (P > 0.05). However, the overall survival (OS) of embryos increased in group #1 (***P < 0.0001) (D). (E, F) These two administrations of 5-FU inhibited the tumor cell proliferation in the zCDX with SGC7901 cells (dyed with red fluorescence using DiL) significantly (**P < 0.01), and there was no difference in cell growth inhibition between group #1 and group #2 (P > 0.05).
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