Fig. 6: LGR5 lineage ablation inhibits organoid and tumor growth.

a, b The outlines of the ex vivo experimental strategy to assess the effects of anticancer drug treatment on organoid initiation, and delineate its temporal aspect (a) or during organoid expansion (b). c The response of wild-type tumor organoids (left) and Lgr5–DTR–GFP mice-derived tumor organoids, with relatively high LGR5 expression (the percentage of LGR5 expression is greater than 1%) (middle) or low LGR5 expression (the percentage of LGR5 expression is lesser than 1%) (right) during regular expansion to DT/sorafenib treatment. −/+: drug treatment during the expansion period; +/+: drug treatment since the initial culture day (unpaired T test). d, e Representative FACS plots showing that LGR5–GFP⁺ cells are depleted by DT treatment, for high LGR5 expression organoid strains (d) and low LGR5 expression organoid strains (e). f Outlines of the experimental strategy used to assess the efficacy of DT/sorafenib/5-FU administration on allograft tumors in mice. g Representative FACS plots from experiments validating the strategy to deplete LGR5⁺ cells. h A representative growth curve showing the volumes of tumors derived from the vehicle control group and the DT-administered group (n = 8, two-way ANOVA). i The weight of tumors from vehicle control, DT, 5-FU, or sorafenib-treated groups, on the day of mice sacrifice (control vs. sorafenib vs. 5-FU vs. DT: 0.34 ± 0.078 g, n = 18 vs. 0.18 ± 0.047 g, n = 15 vs. 0.19 ± 0.033 g, n = 15 vs. 0.15 ± 0.027 g, n = 19). Mean ± SEM. Source data are provided as a Source Data file.