Brusatol inhibits laryngeal cancer cell proliferation and metastasis via abrogating JAK2/STAT3 signaling mediated epithelial-mesenchymal transition

Aims: This study aimed at investigating the role of Brusatol (BR) on human laryngeal squamous carcinoma cell (Hep-2) to study its underlying mechanism through in vitro and in vivo approaches. Materials and method: In the present research, we employed various cell-based assays, such as cell proliferation, apoptosis, cell cycle assessment, migration and invasion assays were used to examine the anti-tumor effect of BR on Hep-2 cells. Immunohistochemistry (IHC), qRT-PCR and Western blotting were performed to study the underlying molecular mechanisms. To validate our in vitro findings we used a subcutaneous tumor-bearing model of Balb/c mice with Hep-2 cells of laryngeal carcinoma (LC) to study the inhibitory effect of BR on Hep-2 cells in vivo. Key findings: The results indicated that BR markedly inhibited the viability, migration and invasion capacity of Hep-2 cells, with no significant toxic effect on normal Human bronchial epithelial cell line (BEAS-2B). Also, BR induced cellular apoptosis by blocking the cells in S phase to suppress cell proliferation. Immunohistochemistry results revealed that BR inhibited the protein expression levels of epithelial-mesenchymal transition (EMT)related markers. Mechanistically, western blotting results exhibited that BR could suppress the protein expression of both JAK2/STAT3 and their phosphorylation levels. Our in vivo experiments further validated the anti-tumor effect of BR on Hep-2 cells in vitro, where BR suppressed the growth of xenograft laryngeal tumor without apparent toxicity. Significance: The present study highlights the anti-LC effect of BR by possibly abrogating JAK2/STAT3 signaling mediated EMT process. BR may be a promising therapeutic candidate for the treatment of LC.

Automated summary

The study explored the role of Brusatol (BR) in human laryngeal squamous carcinoma cells (Hep-2) using in vitro and in vivo approaches. It was found that BR could inhibit the viability, migration, and invasion of Hep-2 cells without significant toxicity to normal cells. Mechanistically, BR induced cell apoptosis and suppressed cell proliferation by blocking cells in S phase. Additionally, BR was shown to inhibit the protein expression levels of epithelial-mesenchymal transition (EMT) related markers.