ß-Elemene alleviates cisplatin resistance in oral squamous cell carcinoma cell via inhibiting JAK2/STAT3 pathway in vitro and in vivo.

ABSTRACT

OBJECTIVE: To investigate the effect of ß-Elemene (ß-Ele) on the cisplatin sensitivity of OSCC cells and its mechanism in vitro and in vivo. METHODS: The human OSCC cell lines Tca-8113 and the cisplatin-resistant cell line Tca-8113-CDDP were cultured with ß-Ele or/and cisplatin. The cytotoxicity of cisplatin or ß-Ele, cell viability, cell cycles and apoptosis were detected. And the expression of JAK2/STAT3 related protein were detected. The xenograft tumor model of OSCC was established in nude mice and treated with cisplatin and/or ß-Ele. The volume and weight of the transplanted tumor was measured, and the expression of p-JAK2 and p-STAT3 and cell apoptosis in the xenograft tumor tissues were detected. RESULTS: The combination of ß-Ele and cisplatin significantly suppressed the cell proliferation, induced cell cycle arrest, promoted the apoptosis of Tca-8113-CDDP cells, and suppressed the activation of JAK2/STAT3 signaling pathway. The rescue experiments suggested that ß-Ele enhanced cisplatin sensitivity via down-regulating JAK2/STAT3 signaling pathway. In vivo, ß-Ele and cisplatin synergistically suppressed the tumor growth and induced apoptosis, and down-regulated the expression of p-JAK2 and p-STAT3. CONCLUSIONS: ß-Ele inhibits the cell viability and enhances the cisplatin sensitivity of OSCC by blocking the activation of JAK/STAT3 signaling pathway in vitro and in vivo, and the combination of ß-Ele and cisplatin maybe a novel treatment for OSCC.