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. 2023 Nov 29;14:7863. doi: 10.1038/s41467-023-43670-9

Fig. 9. Therapeutic targeting of SPINK1 may represent a promising treatment option for chemoresistant HCC.

Fig. 9

a Experimental scheme of Spink1 knockdown in combination with 5-FU treatment in NRasV12+Myr-AKT HTVI HCC model. Lentiviral particles with NTC or encoded Spink1 knockdown (shSpink1) were administered twice at 2- and 3.5-week post HTVI. After tumor initiation, mice were treated with 5-FU (i.p., 20 mg/kg) or DMSO every other day for two weeks. Liver tissues were collected 7-week post HTVI. b Representative images and c quantitative data of liver weights from NTC or shSpink1 mice treated with DMSO or 5-FU. Scale bar = 1 cm. d Kaplan–Meier survival curve showing survival percentage of each annotated group. e Ex vivo limiting dilution analysis for frequency of TICs in cells harvested from NTC or shSpink1 mice with DMSO or 5-FU treatments. f qPCR analysis of the expression of Spink1, stemness and differentiation-related genes, E2F2 and E2F2 target genes. p-values from comparisons to NTC DMSO group were shown in the corresponding boxes. g (Top) Representative image and (bottom) quantitative data of liver tissues from NTC or shSpink1 mice treated with DMSO or 5-FU with Spink1 mRNA staining by RNAScope. Scale bar in low magnification = 50 μm, high magnification = 20 μm. h Cartoon summary of findings. a n = 14–15 mice; b, c n = 5 mice; d n = 7-8 mice; e 19–20 replicates; f n = 10–18 independent experiments; g n = 5 views for Ctrl DMSO group, 3 views for shSpink1 DMSO group, 5 views for Ctrl 5-FU group, 4 views for shSpink1 5-FU group. Data were expressed as mean ± s.e.m. Statistical analysis: (c, f–g) two-way ANOVA, d log-rank test, or e one-sided Person’s χ2 test with 95% confidence intervals. Source data are provided as a Source Data file. Illustration for (a, h) was created using BioRender.com.