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.

背景：越来越多的证据揭示了癌症干细胞 (CSC) 在驱动肿瘤发生和肿瘤复发或转移中的重要作用。选择性靶向 CSC 的治疗策略可能是消除癌症的有效方法。Salinomycin 是一种抗肿瘤剂，被鉴定为几种类型的 CSC 的选择性抑制剂。我们之前报道过盐霉素抑制肝癌干细胞 (LCSC) 的迁移和侵袭。

目的：本研究旨在探讨盐霉素抑制LCSCs干细胞特性的作用及其机制。

方法：从 MHCC97H 细胞中鉴定并富集 LCSC。Salinomycin 用于处理指定浓度的 LCSC。评估球形成能力、化疗耐药性、CSC 表面标志物的表达、杨氏模量和 LCSCs 的致瘤性，以评估沙龙霉素对 LCSCs 的影响。通过蛋白质印迹评估β-连环蛋白的表达。LiCl 用于激活 Wnt/β-catenin 信号通路。

结果：盐霉素抑制 LCSC 的干性特性。此外，盐霉素还可以抑制 LCSCs 中 Wnt/β-catenin 信号的激活。然而，当 Wnt/β-catenin 信号被 LiCl 激活时，LCSCs 的干性特性可以恢复。进一步的研究表明，盐霉素还通过抑制 Wnt/β-catenin 信号通路显着降低 LCSCs 的体内致瘤性。

结论：盐霉素可通过Wnt/β-catenin信号通路抑制干细胞特性并诱导LCSCs分化，为临床上盐霉素可作为靶向LCSCs的肝癌治疗的潜在药物提供证据。