ArticleFrontiers in medicine2025
Carbon-ion radiotherapy induces ferroptosis and M1 macrophage polarization to inhibit the development of gastric cancer by downregulating DHODH.
Article in Frontiers in medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Spatiotemporal dynamics of radioresistance: decoding macrophage-driven radioprotective niches through temporal-spatial reprogramming.Molecular cancer · 2026Review
- The link between macrophage polarization and response to radiotherapy in cancers: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
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Authors and funding
2 authors.
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Abstract
Background: Carbon-ion radiotherapy (CIRT) is an advanced form of high linear energy transfer (LET) radiotherapy that has demonstrated superior biological effectiveness compared to conventional photon therapy in the treatment of various malignancies; however, its role in gastric cancer remains unclear. Dihydroorotate dehydrogenase (DHODH), a key enzyme implicated in cancer progression, has been linked to tumor radiosensitivity. This study aims to investigate whether CIRT inhibits gastric cancer progression via the regulation of DHODH. Methods: Human gastric cancer cell lines (HGC27, AGS) were treated with CIRT (0 Gy, 2 Gy, and 4 Gy). Cell viability, migration, and invasion were assessed with MTT and Transwell assays. Expression of ferroptosis-related markers and DHODH was evaluated using Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Macrophage polarization was assessed by flow cytometry after exposure to tumor-conditioned medium (CM). BALB/c nude mice were subcutaneously injected with AGS cells and randomly assigned to the control, CIRT, and DHODH+CIRT groups. Results: Conclusion: These findings suggest that CIRT promotes ferroptosis and drives M1-like macrophage polarization through DHODH suppression. Targeting DHODH may enhance the therapeutic efficacy of CIRT in gastric cancer.
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