Fig. 6: SAM-dependent methylation synergizes with IKE in tumor growth suppression.

A–C OS-RC-2 cells were cultured in the medium ± IKE, ± methionine, ± FIDAS-5, ± SAM, or ± ADOX as indicated for 24–30 h. A The cellular levels of ROS were respectively quantified at the 24 h. B The lipid ROS levels were determined at the 24 h. C The cell death levels were quantified at the 30 h. IKE, 2 μM; Met, 0.4 mM; SAM, 0.4 mM; FIDAS-5, 5 μM; ADOX, 20 μΜ. D–F The effect of IKE combined with FIDAS-5, SAM, or ADOX on tumors. OS-RC-2 cells were injected into athymic nude mice. Eighteen days after tumor colonization, IKE (40 mg/kg), SAM (250 mg/kg) or ADOX (2 mg/kg) was injected intraperitoneally every 2 day, and FIDAS-5 (20 mg/kg) was injected intragastrically every 2 day. The xenograft tumors were sampled and photographed after 12 days. D The tumors dissected from the mice were photographed. Tumor volume (E) and tumor mass (F) were measured. G The PTGS2 mRNA level in tumor xenografts were determined by qPCR. H Representative immunohistochemical images of MDA, 4-HNE and Ki67 are shown. Scale bars, 10 μm; Representative images of TUNEL staining are shown. Scale bars, 10 μm. I, J, L Relative intensities of MDA, 4-HNE or Ki67 in tumor xenografts were calculated. K The TUNEL-positive ratios in tumor xenografts were calculated. n = 3 biological replicates (A–C); n = 5 mice per group (E, F); n = 3 random samples from each tumor xenograft tissue of the five analyzed mice per group (G); n = 5 random fields from each tumor xenograft tissue of the five analyzed mice per group (I–L); data were represented as mean ± SD with p values determined by one-way ANOVA test (A–C, E–G, I–L). Source data are provided as a Source Data file.