Brusatol Inhibits Laryngeal Cancer Cell Proliferation and Metastasis Via Abrogating JAK2/STAT3 Signaling Mediated Epithelial-Mesenchymal Transition

Abstract

\n Background: Brusatol (BR) is a principal bioactive quassinoid derived from the Chinese medicinal plant Brucea javanica, which has recently been reported to exert notable cytotoxic effects against numerous cancer cell lines. However, the role that BR played in Laryngeal cancer (LC) is seldom known by the public. In the current study, we have investigated the effects of BR on human laryngeal squamous carcinoma cell (Hep-2) and explored its underlying mechanism both in vitro and in vivo experiments. Methods: In the present research, cell proliferation, apoptosis, cycle, migration and invasion assays were used to examine the anti-tumor effect of BR on Hep-2 cells. qRT-PCR, immunohistochemistry (IHC) and Western blotting were performed to study the molecular mechanisms of the action. A subcutaneous tumor-bearing model of Balb/c mice with Hep-2 cells of laryngeal carcinoma was established to observe the inhibitory effect of BR on laryngeal cancer cells in vivo. Results: The results indicated that BR markedly inhibited the viability, migration and invasion of Hep-2 cells in a dose and time-dependent manner, with no significant toxic effect on normal cells BEAS-2B. Also, BR induced cell apoptosis and the cells were blocked in the S phase to suppress cell proliferation. Moreover, the results of IHC showed that BR induction 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 JAK2/STAT3 and their phosphorylation levels. In vivo experiments further confirmed the anti-cancer effect of BR on laryngeal carcinoma cells in vitro, BR suppressed the growth of xenograft laryngeal tumors without apparent toxicity.Conclusions: Consequently, the present study revealed that the anti-LC effect of BR might be closely relevant to abrogation of JAK2/STAT3 signaling mediated EMT process. BR may be a promising therapeutic candidate for the treatment of laryngeal cancer.