Kotowski Ulana, Heiduschka Gregor, Brunner Markus, Erovic Boban M, Martinek Helga, Thurnher Dietmar
Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, A-1090 Vienna, Austria.
Oncol Lett. 2012 Jun;3(6):1326-1330. doi: 10.3892/ol.2012.643. Epub 2012 Mar 14.
Arsenic trioxide (ATO) has been approved for the treatment of relapsed acute promyelocytic leukaemia. The aim of this study was to determine whether ATO would lead to cell death in head and neck squamous cell carcinoma (HNSCC) cell lines and whether it was able to enhance the cytotoxicity of cisplatin, a standard chemotherapeutic agent. The four HNSCC cell lines SCC9, SCC25, CAL27 and FADU were treated with ATO or cisplatin alone or with ATO and cisplatin in combination. Cytotoxicity assays, immunohistochemistry, western blot analysis and flow cytometry were carried out. Possible interactions between the two drugs were calculated using the Chou-Talalay equation. Ther results demonstrated a synergistic cytotoxic effect of the combination of ATO and cisplatin at high doses. The two agents induced apoptosis in all four HNSCC cell lines. In conclusion, this study showed that ATO is a promising therapeutic drug with cytotoxic effects in HNSCC. We demonstrated a synergistic effect in the combined treatment with cisplatin at high doses.
三氧化二砷(ATO)已被批准用于治疗复发的急性早幼粒细胞白血病。本研究的目的是确定ATO是否会导致头颈部鳞状细胞癌(HNSCC)细胞系死亡,以及它是否能够增强标准化疗药物顺铂的细胞毒性。四种HNSCC细胞系SCC9、SCC25、CAL27和FADU分别单独用ATO或顺铂处理,或用ATO与顺铂联合处理。进行了细胞毒性测定、免疫组织化学、蛋白质印迹分析和流式细胞术。使用Chou-Talalay方程计算两种药物之间可能的相互作用。结果表明,高剂量的ATO与顺铂联合具有协同细胞毒性作用。这两种药物在所有四种HNSCC细胞系中均诱导凋亡。总之,本研究表明ATO是一种在HNSCC中具有细胞毒性作用的有前景的治疗药物。我们证明了高剂量下与顺铂联合治疗具有协同作用。