Fig. 6. Subcutaneous tumor models of gastrointestinal stromal tumor (GIST) were established to analyze the synergy effect of Imatinib (IM) and RSL3.

A GIST-T1 cells were subcutaneously transplanted into the dorsolateral side of nude mice. When the subcutaneous tumor volume reached 50 mm³, the mice were randomly divided into four groups (six mice in each group), including the vehicle (DMSO), IM (100 mg/kg), RSL3 (10 mg/kg) or IM combined with RSL3 treatment groups, and then were injected intraperitoneally every there day. All mice were euthanized 18 days later. B Body weight was measured every 3 days until day 18. C The images and quantitative analysis of tumor volume on day 18 after treatment. D–F Western blot analysis of the protein levels of Ki-67, KIT, STUB1, GPX4, and 4-HNE in GIST cell xenograft tumor tissues of mice from vehicle (DMSO), IM, RSL3, and combination treatment groups. n = 3 mice per group. G Immunohistochemical staining representative pictures of hematoxylin-eosin (HE), KIT, STUB1, GPX4, Ki-67, and 4-HNE in GIST cell xenograft tumor tissues of mice from vehicle (DMSO), IM, RSL3, and combination treatment groups. Scale bar, 100 μm. DMSO dimethyl sulfoxide, IM Imatinib, RSL3 Ras-selective lethal small molecule 3, 4-HNE 4-hydroxy-2-nonenal. Significance denoted by: ns not significant, *P < 0.05, **P < 0.01, and ***P < 0.001.