Rhaponticin suppresses the stemness phenotype of gastric cancer stem-like cells CD133+/CD166 + by inhibiting programmed death-ligand 1.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39573998", "kind": "science-record", "revision": 4, "content_hash": "sha256:26272ae91dec1cfc57966d57e4182f9c01d8e388536c5f78cfe046e05a925352", "created_at": "2026-11-01T20:29:50Z", "updated_at": "2026-11-01T22:55:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Rhaponticin suppresses the stemness phenotype of gastric cancer stem-like cells CD133+/CD166 + by inhibiting programmed death-ligand 1.", "doi": "10.1186/s12876-024-03512-4", "pmid": "39573998", "authors": ["Yulong Li", "Yu Zhang", "Jialin Tang"], "journal": "BMC gastroenterology", "year": 2024, "abstract": "BACKGROUND: Gastric cancer stem cells (GCSCs) are key contributors to tumorigenesis, recurrence and metastasis, complicating gastric cancer (GC) treatment. Rhaponticin (RA), a potential novel anticancer drug, has unexplored effects on GCSCs.\nMETHODS: GCSCs were isolated using CD133 and CD166 markers with magnetic bead separation method and then evaluated their response to the IC50 concentrations of RA (16.90 µg/mL for BGC-823 and 22.18 µg/mL for SGC-7901), and effects on cell proliferation, migration, invasion, and stemness were measured. We analyzed the GCSC-related microarray dataset GSE111556 and explored RA's role in restoring programmed cell death ligand 1 (PD-L1) function in CD133+/CD166 + cells post-PD-L1 knockdown. RA's impact on tumour growth and immune microenvironment was assessed in a xenograft mouse model.\nRESULTS: The CD133+/CD166 + subpopulation exhibited stem-like characteristics, with the highest proportion in BGC-823 (38.85%) and SGC-7901 (43.81%) cells. These cells formed tumour spheres and had increased expression of stemness markers Sox2 and Oct-4 (compared to the parental cell line, P < 0.001). RA treatment showed no toxicity to normal GES-1 cells but reduced the viability of CD133+/CD166 + cells in a dose-dependent manner, with IC50 values of 16.90 µg/ml for BGC-823 and 22.18 µg/ml for SGC-7901. RA also decreased the proportion of CD133+/CD166 + cells and their stem-like properties (P < 0.001). Analysis of the GEO database identified PD-L1 as a key target gene of RA, with high expression in GC tissues. Knocking down PD-L1 in CD133+/CD166 + cells and introducing RA did not significantly change PD-L1 expression (P>0.05), suggesting RA's effect may be PD-L1 dependent. In a xenograft mouse model, the tumour size in the RA treatment group was approximately one-sixth that of the CD133+/CD166 + group (P < 0.001). Post-RA treatment, there was an elevation in the expression levels of CD4 and CD8, alongside a reduction in PD-L1 expression (P < 0.001).\nCONCLUSIONS: RA suppresses GCSC stem - like phenotype by inhibiting PD - L1 and enhancing T cell tumour infiltration in the studied models. These findings suggest that RA may have potential for further exploration as a candidate for GC treatment, but extensive preclinical and clinical studies are required to determine its true therapeutic value.", "claims": [{"id": "claim-method", "statement": "Differences between two groups were assessed using independent samples t-test. Comparisons among multiple groups were performed using one-way ANOVA, and two-by-two comparisons were performed using the LSD test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39573998", "locator": "sections[14] \"Statistical analysis\" paragraph 2", "quote": "Differences between two groups were assessed using independent samples t-test. Comparisons among multiple groups were performed using one-way ANOVA, and two-by-two comparisons were performed using the LSD test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used during the present study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39573998", "locator": "sections[27] \"Data availability\" paragraph 2", "quote": "The datasets used during the present study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In a xenograft mouse model, the tumour size in the RA treatment group was approximately one-sixth that of the CD133+/CD166 + group (P < 0.001).", "kind": "quantitative", "target": {"value": 0.001, "unit": "p-value", "tolerance": null, "source": "In a xenograft mouse model, the tumour size in the RA treatment group was approximately one-sixth that of the CD133+/CD166 + group (P < 0.001)."}, "evidence": [{"asset": "source:pmid:39573998", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "In a xenograft mouse model, the tumour size in the RA treatment group was approximately one-sixth that of the CD133+/CD166 + group (P < 0.001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In a xenograft mouse model, the tumour size in the RA treatment group was approximately one-sixth that of the CD133+/CD166 + group (P < 0.001).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:39573998"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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