{
  "abstract": "Although the antidiabetic drug metformin (MET) exhibits anticancer properties, its mechanisms of action in prostate and liver cancer remain unclear. This study aimed to investigate the antiproliferative effects of MET and its impact on key regulatory genes involved in the Wnt, one-carbon metabolism, and p53 signaling pathways in prostate (PC3) and liver (HepG2) cancer cells. Bioinformatic analysis of public RNA-seq datasets (C4-2 and Huh-7) was performed to identify differentially expressed genes following MET exposure. DKK1, MTHFD2, and GADD45A were selected for validation. PC3 and HepG2 cells were treated with MET (5–40 mM) for 24 hours. Cell viability was evaluated using the CCK-8 assay, and RT-qPCR was employed to quantify changes in gene expression.MET inhibited the proliferation of both cell lines in a dose-dependent manner. In MET-treated PC3 cells, DKK1 expression increased up to 2.08-fold, but decreased to 0.6-fold in HepG2 cells. MTHFD2 expression rose in both lines. GADD45A expression was consistently elevated.These results demonstrate that MET has a significant antiproliferative effect on prostate and liver cancer cells. The differential regulation of DKK1 and MTHFD2, along with the consistent upregulation of GADD45A, is associated with MET's antitumor activity. Although this study did not directly test the exact mechanistic causality, the findings suggest that these pathways may play essential roles in MET's action, particularly the activation of the p53 pathway through GADD45A. This study identifies key molecular associations and supports further investigation into MET's therapeutic potential by exploring these altered oncogenic pathways.",
  "abstract_shown": true,
  "affiliations": [
    "Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.",
    "Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran",
    "Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran",
    "Cancer & Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shohreh Fakhari"
    },
    {
      "affs": [
        1
      ],
      "name": "Melika Hekmatnia"
    },
    {
      "affs": [
        2
      ],
      "name": "Mohammad Moradzad"
    },
    {
      "affs": [
        2
      ],
      "name": "Mohammad Reza Rahmani"
    },
    {
      "affs": [
        3
      ],
      "name": "Ali Jalili"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0r2zxtkft3xjc.bib",
  "cited_by": 0,
  "doi": null,
  "fulltext_url": null,
  "id": "0r2zxtkft3xjc",
  "issns": [
    "2251-9637",
    "2251-9645"
  ],
  "landing_url": null,
  "language": "en",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QD1-999"
    ],
    [
      "lcc",
      "QH426-470"
    ]
  ],
  "openalex": null,
  "pdf_url": "http://ijmcmed.org/article-1-2654-en.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-06-01",
  "publisher": "Babol University of Medical Sciences",
  "ris": "https://research.draconitic.com/paper/0r2zxtkft3xjc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:46:48Z",
      "native_id": "4a411a63ea8a49c984d3d4e676bff6cb",
      "source": "doaj",
      "url": null
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "lcc:QH426-470",
      "subfield": "genetics-genomics"
    },
    {
      "field": "chemistry",
      "origin": "lcc:QD1-999",
      "subfield": "general"
    }
  ],
  "title": "Metformin reduces the proliferation of prostate and liver cancer cell lines and alters the expression of DKK1 and GADD45A.",
  "title_text": "Metformin reduces the proliferation of prostate and liver cancer cell lines and alters the expression of DKK1 and GADD45A.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:48Z",
  "url": "https://research.draconitic.com/paper/0r2zxtkft3xjc",
  "venue": "International Journal of Molecular and Cellular Medicine",
  "versions": []
}