甘草酸异甘草次酸镁通过 NF-κB/Twist 信号通路抑制喉癌细胞的进展和上皮间质转化。
Magnesium Isoglycyrrhizinate Induces an Inhibitory Effect on Progression and Epithelial-Mesenchymal Transition of Laryngeal Cancer via the NF-κB/Twist Signaling.
机构信息
Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin City, Heilongjiang Province 150086, People's Republic of China.
出版信息
Drug Des Devel Ther. 2020 Dec 22;14:5633-5644. doi: 10.2147/DDDT.S272323. eCollection 2020.
BACKGROUND
Magnesium isoglycyrrhizinate (MI) was extracted from roots of the plant Glycyrrhiza glabra, which displays multiple pharmacological activities such as anti-inflammation, anti-apoptosis, and anti-tumor. Here, we aimed to investigate the effect of MI on the progression and epithelial-mesenchymal transition (EMT) of laryngeal cancer.
METHODS
Forty laryngeal cancer clinical samples were used. The role of MI in the proliferation of laryngeal cancer cells was assessed by MTT assay, Edu assay and colony formation assay. The function of MI in the migration and invasion of laryngeal cancer cells was tested by transwell assays. The effect of MI on apoptosis of laryngeal cancer cells was determined by cell apoptosis assay. The impact of MI on tumor growth in vivo was analyzed by tumorigenicity analysis using Balb/c nude mice. qPCR and Western blot analysis were performed to measure the expression levels of gene and protein, respectively.
RESULTS
We identified that EMT-related transcription factor Twist was significantly elevated in the laryngeal cancer tissues. The expression of Twist was also enhanced in the human laryngeal carcinoma HEP-2 cells compared with that in the primary laryngeal epithelial cells. The high expression of Twist was remarkably correlated with poor overall survival of patients with laryngeal cancer. Meanwhile, our data revealed that MI reduced cell proliferation, migration and invasion and enhanced apoptosis of laryngeal cancer cells in vitro. Moreover, MI decreased transcriptional activation and the expression levels of NF-κB and Twist, and alleviated EMT in vitro and in vivo. MI remarkably inhibited tumor growth and EMT of laryngeal cancer cells in vivo.
CONCLUSION
MI restrains the progression of laryngeal cancer and induces an inhibitory effect on EMT in laryngeal cancer by modulating the NF-κB/Twist signaling. Our finding provides new insights into the mechanism by which MI inhibits laryngeal carcinoma development, enriching the understanding of the anti-tumor function of MI.
背景
镁甘氨酸（MI）是从甘草的根部提取的，具有多种药理作用，如抗炎、抗凋亡和抗肿瘤。在这里，我们旨在研究 MI 对喉癌进展和上皮间质转化（EMT）的影响。
方法
使用 40 例喉癌临床标本。通过 MTT 测定、Edu 测定和集落形成测定评估 MI 对喉癌细胞增殖的影响。通过 Transwell 测定检测 MI 对喉癌细胞迁移和侵袭的作用。通过细胞凋亡测定确定 MI 对喉癌细胞凋亡的影响。通过使用 Balb/c 裸鼠进行肿瘤发生分析来分析 MI 对体内肿瘤生长的影响。通过 qPCR 和 Western blot 分析分别测量基因和蛋白的表达水平。
结果
我们发现 EMT 相关转录因子 Twist 在喉癌组织中显著升高。与原代喉上皮细胞相比，人喉癌细胞 HEP-2 中的 Twist 表达也增强。Twist 的高表达与喉癌患者的总体生存率差显著相关。同时，我们的数据表明 MI 可减少喉癌细胞的体外增殖、迁移和侵袭，并增强其凋亡。此外，MI 降低了 NF-κB 和 Twist 的转录激活和表达水平，并减轻了体外和体内 EMT。MI 显著抑制了喉癌细胞的体内肿瘤生长和 EMT。
结论
MI 通过调节 NF-κB/Twist 信号通路抑制喉癌细胞的进展，并诱导对喉癌 EMT 的抑制作用。我们的发现为 MI 抑制喉癌发展的机制提供了新的见解，丰富了对 MI 抗肿瘤功能的认识。
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