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29 March 2017 : Laboratory Research  

Synergistic Cytotoxicity of β-Elemene and Cisplatin in Gingival Squamous Cell Carcinoma by Inhibition of STAT3 Signaling Pathway

Chengyi Huang1BDE, Yufeng Yu2ACF*

DOI: 10.12659/MSM.903783

Med Sci Monit 2017; 23:1507-1513

Abstract

BACKGROUND: Cisplatin remains one of the most active agents and is the mainstay of combination chemotherapy regimens against gingival squamous cell carcinoma. However, the efficacy of cisplatin is limited by its high toxicity and the development of drug resistance. β-elemene, isolated from the Chinese herb Rhizoma zedoariahas, is highly effective against malignancies and has low toxicity, but the development of β-elemene sensitizing chemotherapy in targeting the STAT3 signaling pathway remains unexplored in gingival squamous cell carcinoma. The present study was conducted to assess the chemosensitizing effects of b-elemene for enhancing the cytotoxicity of cisplatin in gingival squamous cell carcinoma.

MATERIAL AND METHODS: The gingival squamous cell carcinoma YD-38 cell line was used. MTT assay, clonogenic assay, annexin V/PI apoptosis assay, Western blot analysis, and xenograft model treatment were carried out in vitro and in vivo.

RESULTS: β-elemene significantly enhanced proliferative inhibition and cisplatin induced apoptosis in gingival squamous cell carcinoma. Cisplatin combined with β-elemene decreased the expressions of p-STAT3, p-JAK2, and Bcl-2, and increased the expressions of Bax and caspase-3 significantly compared to cisplatin only treatment, as well as in the xenograft model.

CONCLUSIONS: The results indicated that β-elemene promoted the anti-proliferative and apoptotic effect of cisplatin by inhibiting STAT3 and blocking the JAK2-STAT3 signaling pathway in GSCC in vitro and in vivo.

Keywords: Drugs, Chinese Herbal

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750