Magnesium Isoglycyrrhizinate Induces an Inhibitory Effect on Progression and Epithelial–Mesenchymal Transition of Laryngeal Cancer via the NF-κB/Twist Signaling

Abstract

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.

Keywords:

• laryngeal cancer
• progression
• EMT
• magnesium isoglycyrrhizinate
• Twist
• NF-κB signaling

Abbreviations

EMT, epithelial–mesenchymal transition; MI, Magnesium isoglycyrrhizinate; GA, Glycyrrhizic acid; LEC-P, primary laryngeal epithelial cells; OS, overall survival; IC50, half-maximal inhibitory concentration.

Ethics Approval and Consent to Participate

The patients and healthy controls provided written informed consent, and that the Ethics Committee of The Second Affiliated Hospital, Harbin Medical University approved this study. All animal experiments in this study were approved according to the standards of Care and Use enacted by Laboratory Animals of The Second Affiliated Hospital, Harbin Medical University, and was approved by the Animal Ethics Committee of The Second Affiliated Hospital, Harbin Medical University.

Disclosure

All the authors have declared no potential conflicts of interest for this research.