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

Autor: Yulong Li, Yu Zhang, Jialin Tang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: BMC Gastroenterology, Vol 24, Iss 1, Pp 1-14 (2024)
Druh dokumentu: article
ISSN: 1471-230X
DOI: 10.1186/s12876-024-03512-4
Popis: 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 0.05), 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
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