Eder-Czembirek Christina, Czembirek Cornelia, Erovic Boban M, Selzer Edgar, Turhani Dritan, Vormittag Laurenz, Thurnher Dietmar
Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Oncol Rep. 2005 Sep;14(3):667-71.
Betulinic acid (BetA), a new experimental cytotoxic compound that is active against human melanoma cells and neuroectodermal tumor cells, has recently been shown to be also effective against head and neck squamous carcinoma cells (HNSCC). In this study we investigated BetA in combination with cisplatin in squamous cell carcinoma cell lines of the tongue. SCC25 and SCC9 were treated with BetA and/or cisplatin. Cells were counted with an automated analyzing system. Caspase activation was determined using the M30 Cyto-Death ELISA, expression of the anti-apoptotic protein Mcl-1 by Western blot analysis. Visualization of apoptotic cells was achieved by immunohistochemistry. Synergistic cytotoxic effect and the induction of apoptosis under combined treatment was observed in SCC25 cells only after 24 or 48 h, whereas treatment of SCC25 cells for 72 h with BetA and cisplatin showed antagonism or subadditive effects. In SCC9 cells, antagonism occurred over an increase of dose and time during treatment. Furthermore, we could not demonstrate a significant alteration in the expression of the anti-apoptotic protein, Mcl-1. Our in vitro data demonstrate that BetA seems to be an unlikely candidate for combination with cisplatin in the treatment of head and neck cancer.
桦木酸（BetA）是一种新型实验性细胞毒性化合物，对人类黑色素瘤细胞和神经外胚层肿瘤细胞具有活性，最近还被证明对头颈部鳞状细胞癌（HNSCC）细胞也有效。在本研究中，我们研究了桦木酸与顺铂联合用于舌鳞状细胞癌细胞系的情况。用桦木酸和/或顺铂处理SCC25和SCC9细胞。使用自动分析系统对细胞进行计数。使用M30细胞死亡ELISA测定半胱天冬酶激活情况，通过蛋白质印迹分析抗凋亡蛋白Mcl-1的表达。通过免疫组织化学实现凋亡细胞的可视化。仅在24或48小时后，在SCC25细胞中观察到联合治疗下的协同细胞毒性作用和凋亡诱导，而用桦木酸和顺铂处理SCC25细胞72小时显示出拮抗或亚相加作用。在SCC9细胞中，在治疗期间随着剂量和时间的增加出现拮抗作用。此外，我们未能证明抗凋亡蛋白Mcl-1的表达有显著变化。我们的体外数据表明桦木酸似乎不太可能成为与顺铂联合用于治疗头颈癌的候选药物。
