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. 2021 Jun 1;131(11):e143377. doi: 10.1172/JCI143377

Figure 6. Inhibition of α-(1,2) fucosylation by 2DGal increases the efficacy of sorafenib and eradicates tumor-initiating cells.

Figure 6

(A) Schematic representation of the effects of 2DGal and sorafenib on Huh7 HCC cell proliferation (10 mM 2DGal and 4 μM sorafenib) and HCC patient-derived organoids (HCC-HK P1 and HCC-HK P2, 10 mM 2DGal and 2 μM sorafenib; HCC10, 10 mM 2DGal and 4 μM sorafenib) after 72 hours. (B) CellTiter Glo analysis found that Huh7 cells with FUT1 overexpression (OE) responded to a combination of 2DGal and sorafenib more significantly than either drug alone when compared with the empty vector (EV) control (1-way ANOVA). (C) In vitro limiting-dilution assays of Huh7 cells cultured in low glucose treated with 2DGal (10 mM) (pairwise tests for differences in stem cell frequencies). (D) Western blot analysis of FUT1 expression in HCC-HK P1, HCC-HK P2, and HCC10. (E) CellTiter Glo analysis found that FUT1-expressing HCC organoids (HCC-HK P2 and HCC10) responded to a combination of 2DGal and sorafenib more significantly than either drug alone when compared with HCC-HK-P1 (1-way ANOVA). (F) Strategy for testing the effects of 2DGal and sorafenib in NRAS+AKT+SB HTVI–driven HCC immunocompetent mouse models. (G) Ex vivo limiting-dilution assay of HCC tumor cells harvested from the HTVI mouse models (pairwise tests for differences in stem cell frequencies). The data shown in B–E and G are representative of 3 independent experiments. 2DGal, 2-deoxy-D-galactose; LDA, limiting dilution assay; SB, sleeping beauty; HTVI, hydrodynamic tail vein injection; Combo, combination. *P < 0.05; **P < 0.01; ****P < 0.0001. NS, not significant.