{
  "abstract": "BackgroundTumor-cell-derived inflammatory signals can alter endothelial activation and barrier integrity in triple-negative breast cancer. Whether pretreating tumor cells with Sanhuang Decoction (SHD) changes the subsequent conditioned-medium (CM)-associated endothelial phenotype remains unclear.MethodsMDA-MB-231 cells were exposed to SHD, washed twice with phosphate-buffered saline, and cultured in fresh drug-free medium before CM collection. Tumor-cell migration, CXCL8 mRNA, and viable donor-cell-normalized CXCL8 secretion were assessed, with selected CCK-8 and CXCL8 validation in MDA-MB-468, BT-549, and Hs578T cells. Human umbilical vein endothelial cells (HUVECs) were exposed to Control-CM, 231-CM, or CM from SHD-pretreated MDA-MB-231 cells and evaluated by RNA sequencing, RT-qPCR, western blotting, immunofluorescence, FITC-dextran permeability, CellTracker-based transendothelial migration, and representative transmission electron microscopy. A direct-SHD HUVEC western blot control and the PI3K agonist 740 Y-P were used to examine direct-exposure effects and pathway participation. Public-data, LC-HRMS/MS profiling, HPLC-DAD emodin marker analysis, network, and enrichment analyses provided study context.ResultsSHD reduced MDA-MB-231 migration, decreased CXCL8 mRNA across the TNBC validation panel, and reduced viable donor-cell-normalized CXCL8 secretion in all four TNBC cell lines, most consistently at 6 mg/mL. In HUVECs, SHD6-CM was associated with opposite-direction changes in a subset of 231-CM-associated transcriptomic features involving cytoskeletal, vascular-wall interaction, PI3K/AKT, and junction-related programs. It reduced VCAM-1, ICAM-1, and PI3K/AKT phosphorylation while increasing ZO-1, VE-cadherin, and Occludin-related readouts. Direct SHD exposure did not reproduce this coordinated HUVEC protein pattern. SHD6-CM was also associated with lower FITC-dextran permeability and fewer CellTracker Green-positive MDA-MB-231 cells crossing the endothelial monolayer. Addition of 740 Y-P attenuated these molecular and functional changes, consistent with partial PI3K/AKT participation.ConclusionCM from SHD-pretreated MDA-MB-231 cells was associated with reduced endothelial inflammatory activation and improved barrier-related readouts in this in vitro model. CXCL8 remains an associated candidate mediator within a multicomponent secretory response, rather than an established sole mediator, and pathway-specific experiments are needed to define the contribution of PI3K/AKT.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "Ke Hong"
    },
    {
      "name": "Shuqin Li"
    },
    {
      "name": "Cong Wang"
    },
    {
      "name": "Xinhe Liu"
    },
    {
      "name": "Chang Yao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/47p8sryzq9vrm.bib",
  "cited_by": 0,
  "doi": "10.3389/fmolb.2026.1965244",
  "fulltext_url": null,
  "id": "47p8sryzq9vrm",
  "issns": [
    "2296-889X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fmolb.2026.1965244",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "biochemistry/general"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/47p8sryzq9vrm.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T06:20:13Z",
      "native_id": "10.3389/fmolb.2026.1965244",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fmolb.2026.1965244"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "journal-openalex:1312|Protein Structure and Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Conditioned medium from Sanhuang Decoction-pretreated MDA-MB-231 cells attenuates endothelial inflammation and barrier dysfunction",
  "title_text": "Conditioned medium from Sanhuang Decoction-pretreated MDA-MB-231 cells attenuates endothelial inflammation and barrier dysfunction",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T00:20:34Z",
  "url": "https://research.draconitic.com/paper/47p8sryzq9vrm",
  "venue": "Frontiers in Molecular Biosciences",
  "versions": []
}