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2016 ; 16
(1
): 896
Nephropedia Template TP
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Salinomycin inhibits metastatic colorectal cancer growth and interferes with
Wnt/?-catenin signaling in CD133(+) human colorectal cancer cells
#MMPMID27855654
Klose J
; Eissele J
; Volz C
; Schmitt S
; Ritter A
; Ying S
; Schmidt T
; Heger U
; Schneider M
; Ulrich A
BMC Cancer
2016[Nov]; 16
(1
): 896
PMID27855654
show ga
BACKGROUND: The polyether antibiotic Salinomycin (Sal) is regarded as an
inhibitor of cancer stem cells. Its effectiveness on human colorectal cancer
(CRC) cells in vitro has been demonstrated before. The aim of this study was to
establish a murine model to investigate the effectiveness of Sal in vivo.
Furthermore, we investigated the impact of Sal on Wnt/?-catenin signaling in
human CD133(+) CRC cells. METHODS: The two murine CRC cell lines MC38 and CT26
were used to analyze the impact of Sal on tumor cell proliferation, viability,
migration, cell cycle progression and cell death in vitro. For in vivo studies,
CT26 cells were injected into syngeneic BALB/c mice to initiate (i) subcutaneous,
(ii) orthotopic, or (iii) metastatic CRC growth. Sal was administered daily,
5-Fluoruracil served as a control. For mechanistic studies, the CD133(+)and
CD133(-) subpopulations of human CRC cells were separated by flow cytometry and
separately exposed to increasing concentrations of Sal. The impact on
Wnt/?-catenin signaling was determined by Western blotting and quantitative PCR.
RESULTS: Sal markedly impaired tumor cell viability, proliferation and migration,
and induced necrotic cell death in vitro. CRC growth in vivo was likewise
inhibited upon Sal treatment. Interference with Wnt signaling and reduced
expression of the Wnt target genes Fibronectin and Lgr5 indicates a novel
molecular mechanism, mediating anti-tumoral effects of Sal in CRC. CONCLUSION:
Sal effectively impairs CRC growth in vivo. Furthermore, Sal acts as an inhibitor
of Wnt/?-catenin signaling. Thus, Salinomycin represents a promising candidate
for clinical CRC treatment.