Ferroptosis suppression by MYC confers oxaliplatin resistance in colorectal cancer via FTH1 and GPX4.

Yucheng Wang, Yulan Chen, Che Li, Jin Yang

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Article in Cancer chemotherapy and pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 authors.

Yucheng WangCollege of Life Sciences, Shanghai Normal University, Shanghai, 201418, China.

Yulan ChenCollege of Life Sciences, Shanghai Normal University, Shanghai, 201418, China.

Che LiCollege of Life Sciences, Shanghai Normal University, Shanghai, 201418, China.

Jin YangCollege of Life Sciences, Shanghai Normal University, Shanghai, 201418, China. yangjin@shnu.edu.cn.ORCID https://orcid.org/0009-0003-8458-7071

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6 · The paper itself

Abstract

purposeOxaliplatin resistance remains a major obstacle in the treatment of colorectal cancer (CRC). This study aimed to determine whether MYC contributes to oxaliplatin resistance by regulating ferroptosis and to clarify the downstream mechanisms involving FTH1 and GPX4.

methodsParental CRC cell lines, including HCT116, HT-29 and SW480, together with oxaliplatin-resistant HCT116-R cells, were used. MYC expression was manipulated by knockdown or overexpression. Oxaliplatin sensitivity was evaluated using CCK-8 assays and IC50 analysis. Intracellular Fe

resultsMYC knockdown significantly increased oxaliplatin sensitivity in both parental and resistant CRC cells and elevated intracellular Fe

conclusionMYC promotes oxaliplatin resistance in CRC cells, at least in part, by transcriptionally upregulating FTH1 and GPX4 and suppressing ferroptosis-associated cell death. The MYC-FTH1/GPX4-ferroptosis axis may represent a potential therapeutic target for overcoming oxaliplatin resistance in CRC.

Indexed as

Antineoplastic AgentsColorectal NeoplasmsDrug Resistance, NeoplasmFerritinsFerroptosisOxaliplatinOxidoreductasesPhospholipid Hydroperoxide Glutathione PeroxidaseProto-Oncogene Proteins c-mycCell Line, TumorGene Expression Regulation, NeoplasticHCT116 CellsHT29 CellsHumansReactive Oxygen SpeciesAntineoplastic AgentsFerritinsFTH1 protein, humanMYC protein, humanOxaliplatinOxidoreductasesPhospholipid Hydroperoxide Glutathione PeroxidaseProto-Oncogene Proteins c-mycReactive Oxygen SpeciesChemoresistanceFerroptosisFTH1GPX4MYC

Identifiers

PMID42560559

DOI10.1007/s12032-023-02130-6

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