{
  "abstract": "Background\n\nErlotinib, an epidermal growth factor receptor (EGFR) small molecule inhibitor approved by the Food and Drug Administration (FDA) for the treatment of pancreatic cancer, faces significant drug resistance challenges. To address this, we investigated the potential of agrimoniin, a key active compound in the traditional Chinese medicine Agrimonia pilosa, which is known for its potent anticancer activity. This study aims to explore the combined effect of these two compounds in pancreatic cancer.Methods\n\nWe sought to verify the combined inhibitory effect of pancreatic cancer by agrimoniin and erlotinib in vitro and in vivo using various assays, including subcutaneous xenograft experiments and western blot. Single-cell RNA sequencing, bioinformatics, western blot, and lactic acid assays were performed to study how agrimoniin and erlotinib affect the tumor microenvironment and aerobic glycolysis. Finally, using signal pathway inhibitors/agonists, lactic acid assays, and Western blot, we aimed to reveal two positive feedback loops between signal pathways and lactic acid production.Results\n\nAgrimoniin combines with erlotinib to inhibit proliferation of pancreatic cancer cells. Together, they effectively suppress signal interactions between tumor cells, stromal cells, and macrophages within subcutaneous tumors. Simultaneously, they jointly inhibit aerobic glycolysis and lactic acid production in pancreatic cancer. Notably, this study proposes two potentially novel positive feedback loops between the PI3K/AKT/HIF-1α/HK2, MEK/ERK/HIF-1α/HK2 signaling pathways and lactic acid production.Conclusions\n\nThe combination of agrimoniin and erlotinib suppresses signal interactions between tumor cells, macrophages, and stromal cells in the tumor microenvironment, reprograms aerobic glycolysis, disrupts two positive feedback loops, thereby cooperatively inhibiting the proliferation of pancreatic cancer cells. This study provides a theoretical basis for agrimoniin as a sensitizer or resistance-reversing agent for erlotinib, and offers new insights and potential targets for pancreatic cancer drug development.",
  "abstract_shown": true,
  "affiliations": [
    "School of Medicine, Nanjing University of Chinese Medicine, Nanjing, China.",
    "Key Laboratory of Drug Target and Drug for Degenerative Disease, School of Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210023, Jiangsu, China.",
    "Ili & Jiangsu Joint Institute of Health, The Friendship Hospital of Ili Kazakh Autonomous Prefecture, Yining, China.",
    "Endoscopy Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.",
    "College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China.",
    "School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China.",
    "School of Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.",
    "Singleron Biotechnologies, Nanjing, China.",
    "Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China. zhuyijssry@njmu.edu.cn.",
    "Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China. zhangjingjing@njmu.edu.cn.",
    "School of Medicine, Nanjing University of Chinese Medicine, Nanjing, China. zhulifeng@njucm.edu.cn.",
    "Key Laboratory of Drug Target and Drug for Degenerative Disease, School of Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210023, Jiangsu, China. zhulifeng@njucm.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xiongfei Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xinyi Xia"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Yan Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Huanhuan Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Huiying Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yutong Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Lei Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Shaojun Wang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Qinlong Dai"
    },
    {
      "affs": [
        4
      ],
      "name": "Ling Gu"
    },
    {
      "affs": [
        5
      ],
      "name": "Yiwen Chen"
    },
    {
      "affs": [
        5
      ],
      "name": "Xinye Dong"
    },
    {
      "affs": [
        0
      ],
      "name": "Beili Xi"
    },
    {
      "affs": [
        0
      ],
      "name": "Li Tao"
    },
    {
      "affs": [
        0
      ],
      "name": "Yang Hua"
    },
    {
      "affs": [
        6
      ],
      "name": "Zhihan Zhang"
    },
    {
      "affs": [
        7
      ],
      "name": "Xinyue Tian"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuyan Ling"
    },
    {
      "affs": [
        0
      ],
      "name": "Tingting Xu"
    },
    {
      "affs": [
        8
      ],
      "name": "Yi Zhu"
    },
    {
      "affs": [
        9
      ],
      "name": "Jingjing Zhang"
    },
    {
      "affs": [
        10,
        11
      ],
      "name": "Lifeng Zhu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2h0y8g171kx7v.bib",
  "cited_by": 0,
  "doi": "10.1186/s11658-026-01000-z",
  "fulltext_url": "https://europepmc.org/articles/PMC13753132",
  "id": "2h0y8g171kx7v",
  "issns": [
    "1425-8153",
    "1689-1392"
  ],
  "landing_url": "https://europepmc.org/article/MED/43009796",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Pancreatic and Hepatic Oncology Research"
    ]
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  "openalex": "W7202125079",
  "pdf_url": "https://europepmc.org/articles/PMC13753132?pdf=render",
  "pmcid": "PMC13753132",
  "pmid": "43009796",
  "published": "2026-08-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2h0y8g171kx7v.ris",
  "sources": [
    {
      "first_seen": "2026-11-12T15:22:43Z",
      "native_id": "MED:43009796",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/43009796"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Pancreatic and Hepatic Oncology Research",
      "subfield": "oncology"
    }
  ],
  "title": "Agrimoniin combines with erlotinib to inhibit the proliferation of pancreatic cancer cells by suppressing signal interactions in the tumor microenvironment and disrupting two positive feedback loops involving lactic acid production.",
  "title_text": "Agrimoniin combines with erlotinib to inhibit the proliferation of pancreatic cancer cells by suppressing signal interactions in the tumor microenvironment and disrupting two positive feedback loops involving lactic acid production.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-13T03:20:45Z",
  "url": "https://research.draconitic.com/paper/2h0y8g171kx7v",
  "venue": "Cellular & molecular biology letters",
  "versions": []
}