{
  "abstract": "Cisplatin resistance remains a major therapeutic challenge in esophageal squamous cell carcinoma (ESCC). Here, we investigated the antitumor effects and underlying mechanisms of Huayu Wan (HYW) in cisplatin-resistant ESCC. HYW markedly inhibited the growth of cisplatin-resistant human KYSE150 and murine mEC25 cells and induced a ferroptotic phenotype characterized by reactive oxygen species accumulation, increased intracellular iron, glutathione depletion, lipid peroxidation, and reduced GPX4 expression. Ferrostatin-1 partially reversed HYW-induced cytotoxicity. HYW also promoted immunogenic cell death-associated changes, including extracellular ATP and HMGB1 release and cell-surface calreticulin exposure. Mechanistically, HYW increased p53 expression and impaired the SLC7A11/GCLC-dependent cystine–glutathione antioxidant system, whereas GCLC overexpression and P53 inhibition partially restored redox homeostasis and cell survival. In parallel, HYW suppressed AKT–mTOR signaling and promoted NCOA4-associated ferritinophagy, as evidenced by increased NCOA4 and LC3-II and decreased FTH expression. Pharmacological inhibition of autophagy and NCOA4 knockdown attenuated iron accumulation and HYW-induced cytotoxicity. In cisplatin-resistant syngeneic tumors, HYW suppressed tumor growth with generally acceptable systemic tolerability, enhanced ferroptosis- and immunogenic stress-associated changes, reduced PD-L1 expression, and increased CD8 ⁺ T-cell infiltration. Moreover, HYW combined with anti-PD-1 treatment produced greater antitumor effects than either monotherapy. These findings suggest that HYW promotes ferroptosis through coordinated disruption of glutathione metabolism and NCOA4-associated ferritinophagy while enhancing antitumor immune responses in cisplatin-resistant ESCC.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Thoracic Surgery, Shaoxing People’s Hospital, School of Medicine, Shaoxing University",
    "Department of Cardiac and Great Vascular Surgery, Shaoxing People’s Hospital, School of Medicine, Shaoxing University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ting Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Bin Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Haiyong Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianyi Ding"
    },
    {
      "affs": [
        0
      ],
      "name": "Yangjun Xu"
    },
    {
      "affs": [
        1
      ],
      "name": "Jianfeng Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Lingjun Dong"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiang Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Guangmao Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhupeng Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dft3qekwd0nj2.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1967436",
  "fulltext_url": null,
  "id": "dft3qekwd0nj2",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1967436/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Ferroptosis and cancer prognosis"
    ]
  ],
  "openalex": "W7223902145",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-27",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/dft3qekwd0nj2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1967436",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1967436/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
    }
  ],
  "title": "Huayu Wan induces ferroptosis and enhances anti-PD-1 efficacy in cisplatin-resistant esophageal squamous cell carcinoma",
  "title_text": "Huayu Wan induces ferroptosis and enhances anti-PD-1 efficacy in cisplatin-resistant esophageal squamous cell carcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:17Z",
  "url": "https://research.draconitic.com/paper/dft3qekwd0nj2",
  "venue": "Frontiers in Immunology",
  "versions": []
}