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二氢杨梅素通过拮抗 Wnt/β-连环蛋白信号通路在鼻咽癌细胞中发挥抗肿瘤活性。

Dihydromyricetin Exhibits Antitumor Activity in Nasopharyngeal Cancer Cell Through Antagonizing Wnt/β-catenin Signaling.

机构信息

The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.

The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.

出版信息

Integr Cancer Ther. 2021 Jan-Dec;20:1534735421991217. doi: 10.1177/1534735421991217.

DOI:10.1177/1534735421991217
PMID:33724059
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7975991/
Abstract

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.

摘要

背景

癌症干细胞（CSCs）已被证明在多种癌症的生物学过程中发挥着重要作用。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已经得到证实。失调的 Wnt/β-连环蛋白信号通路是导致化疗耐药和维持 CSCs 样特征的重要因素。本研究旨在全面研究二氢杨梅素（DMY），一种天然黄酮类药物，对顺铂（cis）耐药和鼻咽癌干细胞特性的作用。

方法

本研究在体外和体内全面研究了 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

在平行实验中，DMY 的加入增强了 cis 耐药鼻咽癌细胞系（Hone1/cis 和 CNE1/cis）中 cis 的生长抑制作用。功能实验表明，DMY 显著降低了鼻咽细胞的干细胞特性，如集落和肿瘤球形成。体内数据表明，DMY 的给药显著抑制了 Hone1 CSCs 形成的肿瘤异种移植的生长。此外，DMY 可以破坏 Wnt/β-连环蛋白信号通路，并调节鼻咽癌细胞中下游蛋白的表达。

结论

本研究通过阻断 Wnt/β-连环蛋白信号通路阐明了 DMY 在鼻咽癌中的抗肿瘤活性。因此，DMY 可能成为治疗鼻咽癌的一种新的治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6542/7975991/218cb8537c6d/10.1177_1534735421991217-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6542/7975991/a3bf09816166/10.1177_1534735421991217-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6542/7975991/5fadeb38aeca/10.1177_1534735421991217-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6542/7975991/f2019d1b0568/10.1177_1534735421991217-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6542/7975991/453dd61cf94f/10.1177_1534735421991217-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6542/7975991/84546211936c/10.1177_1534735421991217-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6542/7975991/218cb8537c6d/10.1177_1534735421991217-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6542/7975991/a3bf09816166/10.1177_1534735421991217-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6542/7975991/5fadeb38aeca/10.1177_1534735421991217-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6542/7975991/f2019d1b0568/10.1177_1534735421991217-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6542/7975991/453dd61cf94f/10.1177_1534735421991217-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6542/7975991/84546211936c/10.1177_1534735421991217-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6542/7975991/218cb8537c6d/10.1177_1534735421991217-fig6.jpg

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