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

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

BMC Gastroenterol

Department of Gastroenterology, Shaanxi Provincial People's Hospital, No. 256 Friendship West Road, Beilin District, Xi'an, Shaanxi, 710068, China.

Published: November 2024

AI Article Synopsis

  • Gastric cancer stem cells (GCSCs) are crucial for tumor growth and recurrence, making them important targets for treatments; Rhaponticin (RA) is a new anticancer drug that may affect GCSCs' properties.
  • In experiments, isolated GCSCs showed stem-like traits and were sensitive to RA, which decreased their viability and stemness markers without harming normal cells; RA showed a pronounced effect in two specific gastric cancer cell lines.
  • Additionally, RA appears to target the PD-L1 gene, and studies in a mouse model demonstrated that RA significantly reduced tumor size compared to untreated GCSCs, suggesting potential therapeutic benefits for gastric cancer patients.

Article 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.

Methods: 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.

Results: 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).

Conclusions: 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583647PMC
http://dx.doi.org/10.1186/s12876-024-03512-4DOI Listing

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