Background:

Cancer stem cells (CSCs) have been demonstrated to play a vital role in a diversity of biological processes in cancers. With the emergence of new evidence, the important function of CSCs in the formation of multidrug resistance of nasopharyngeal cancer has been demonstrated. Dysregulated Wnt/β-catenin signaling pathway is an important contributor to chemoresistance and maintenance of CSCs-like characteristics. This research aims to investigate comprehensively the function of dihydromyricetin (DMY), a natural flavonoid drug, on the cisplatin (cis) resistance and stem cell properties of nasopharyngeal cancer.

Methods:

In this study, the functional role of DMY in nasopharyngeal cancer progression was comprehensively investigated in vitro and in vivo, and then its relationship with CSCs-like phenotypes and multiple oncogenes was analyzed.

Results:

In parallel assays, the growth inhibitory action of cis was enhanced by the addition of DMY in cis-resistant nasopharyngeal cancer cell lines (Hone1/cis and CNE1/cis). Functional assays showed that DMY markedly diminished the stem cell properties of nasopharyngeal cells, such as colony and tumor-sphere formation. In vivo data showed that the growth of Hone1 CSCs formed tumor xenograft was inhibited significantly by the administration of DMY. Additionally, DMY could impair the Wnt/β-catenin signaling pathway and regulate the expression of downstream proteins in nasopharyngeal cancer cells.

Conclusions:

Our study clarified the anti-tumor activity of DMY through blocking the Wnt/β-catenin signaling pathway in nasopharyngeal cancer. Therefore, DMY could be a novel therapeutic agent for nasopharyngeal cancer treatment.

中文翻译：

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二氢杨梅素通过拮抗 Wnt/β-catenin 信号通路在鼻咽癌细胞中表现出抗肿瘤活性

背景：

癌症干细胞 (CSC) 已被证明在癌症的多种生物过程中发挥着至关重要的作用。随着新证据的出现，CSCs在鼻咽癌多药耐药形成中的重要作用得到证实。失调的 Wnt/β-catenin 信号通路是化学抗性和维持 CSC 样特征的重要因素。本研究旨在全面研究天然黄酮类药物二氢杨梅素（DMY）对鼻咽癌顺铂（cis）耐药性和干细胞特性的作用。

方法：

本研究在体外和体内综合研究了DMY在鼻咽癌进展中的功能作用，然后分析了其与CSCs样表型和多种癌基因的关系。

结果：

在平行测定中，通过在顺式抗性鼻咽癌细胞系（Hone1/cis 和 CNE1/cis）中添加 DMY 来增强顺式的生长抑制作用。功能分析表明，DMY 显着降低了鼻咽细胞的干细胞特性，例如集落和肿瘤球的形成。体内数据表明，DMY 的给药显着抑制了 Hone1 CSCs 形成的肿瘤异种移植物的生长。此外，DMY 可以损害 Wnt/β-catenin 信号通路并调节鼻咽癌细胞中下游蛋白质的表达。

结论：

我们的研究通过阻断鼻咽癌中的 Wnt/β-catenin 信号通路阐明了 DMY 的抗肿瘤活性。因此，DMY可能成为鼻咽癌治疗的新型治疗剂。