Fig. 6: Synergistic effects of ISRIB or DTHIB in targeting oxaliplatin resistance.

a Experimental design for assessing combination therapies in oxaliplatin-sensitive (parental) and oxaliplatin-resistant (TDOXR) mouse models. b Quantification of tumor burden in parental xenografts of nude mice treated with vehicle control, oxaliplatin (5 mg/kg, three times per week), alone or in combination with ISRIB (4 mg/kg, once daily for two consecutive weeks) or DTHIB (5 mg/kg, once daily for two consecutive weeks) (n = 5 mice per group). c Tumor burden quantification in TDOXR xenografts of nude mice treated with vehicle control, oxaliplatin (5 mg/kg, three times per week), alone or in combination with DTHIB (5 mg/kg, once daily for two consecutive weeks) (n = 5 mice per group). d Quantification of the SG index as detected by UBPA2L or G3BP1, and CC3-positive area or TUNEL-positive area from xenograft tumors in (b). e Quantification of the SG index as detected by UBPA2L or G3BP1, and CC3-positive area or TUNEL-positive area from xenograft tumors in c. f Schematic of generation of spontaneous GC mouse model. Tamoxifen-induced recombination of mutant alleles is mediated using a gastric-specific Claudin18-Cre^ERT2 strain. g Experimental design for tamoxifen-induced recombination and oxaliplatin treatment in spontaneous GC mouse model. h Representative HE staining, and IF staining of UBAP2L, E-cadherin, CC3, and TUNEL in spontaneous GC tumors according to their response to oxaliplatin treatment. The dashed line indicates the magnified area. Scale bars, 50 μm (UBAP2L/Ecadherin), otherwise 20 μm. P values determined by two-way ANOVA with Bonferroni’s post hoc test (b, c) or one-way ANOVA with Bonferroni’s post hoc test (d, e). Data are represented as the mean ± s.e.m (d, e). Data are pooled biological replicates (b, c, h).