Title:Salinomycin Suppresses Tumorigenicity of Liver Cancer Stem Cells and Wnt/Beta-catenin Signaling
Volume: 16
Issue: 5
Author(s): Qiuping Liu , Jinghui Sun, Qing Luo, Yang Ju and Guanbin Song*
Affiliation:
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030,China
Keywords:
Liver cancer stem cells, salinomycin, stemness, differentiation, Wnt/β-catenin signaling pathway, liver cancer therapy.
Abstract:
Background: Accumulating evidence has revealed the important role of Cancer Stem Cells
(CSCs) in driving tumor initiation and tumor relapse or metastasis. Therapeutic strategies that selectively
target CSCs may be effective approaches to eliminate cancer. Salinomycin, an antitumor agent,
was identified as a selective inhibitor of several types of CSCs. We previously reported that salinomycin
inhibits the migration and invasiveness of Liver Cancer Stem Cells (LCSCs).
Objective: This study was conducted to explore the role of salinomycin in suppressing the stemness
properties of LCSCs and the mechanism.
Methods: LCSCs were identified and enriched from MHCC97H cells. Salinomycin was used to treat
LCSCs at the indicated concentrations. Sphere formation ability, chemotherapy resistance, expression
of CSC surface markers, Young’s modulus and tumorigenicity of LCSCs were assessed to evaluate the
effect of salionmycin on LCSCs. The expression of β-catenin was evaluated by western blotting. LiCl
was used to activate the Wnt/β-catenin signaling pathway.
Results: Salinomycin suppresses the stemness properties of LCSCs. Moreover, salinomycin could also
inhibit the activation of Wnt/β-catenin signaling in LCSCs. Nevertheless, the stemness properties of
LCSCs could be recovered when Wnt/β-catenin signaling was activated by LiCl. Further studies demonstrated
that salinomycin also significantly reduces the tumorigenicity of LCSCs in vivo by suppressing
the Wnt/β-catenin signaling pathway.
Conclusion: Salinomycin could suppress stemness properties and induce differentiation of LCSCs
through the Wnt/β-catenin signaling pathway, which provides evidence that salinomycin may serve as a
potential drug for liver cancer therapy targeting LCSCs in the clinic.
