Department of Otolaryngology, University of Leipzig, Leipzig, Germany.
Anticancer Res. 2013 Jun;33(6):2415-24.
The hedgehog signaling pathway (HH) is involved in tumorigenesis in a variety of human malignancies. In head and neck squamous cell carcinomas (HNSCC), Hh overexpression was associated with poor prognosis. Therefore, we analyzed the effect of Hh signaling blockade with cyclopamine on colony formation of cells from HNSCC samples.
HNSCC biopsies were cultured alone for reference or with serial dilutions of cyclopamine (5-5,000 nM), docetaxel (137.5-550 nM), or cisplatin (1,667-6,667 nM) and their binary combinations. Cytokeratin-positive colonies were counted after fluorescent staining.
Cyclopamine concentration-dependently inhibited HNSCC ex vivo [(IC50) at about 500 nM]. In binary combinations, cyclopamine additively enhanced the suppressive effects of cisplatin and docetaxel on HNSCC colony formation.
Our findings define SMO--a Hh component- as a potential target in HNSCC and suggest the utility of Hh targeting in future multimodal treatment regimens for HNSCC.
刺猬信号通路（HH）参与多种人类恶性肿瘤的发生。在头颈部鳞状细胞癌（HNSCC）中，HH 的过表达与预后不良相关。因此，我们分析了用环巴胺阻断 HH 信号对 HNSCC 样本细胞集落形成的影响。
HNSCC 活检单独培养作为对照，或与环巴胺（5-5000 nM）、多西他赛（137.5-550 nM）或顺铂（1667-6667 nM）的系列稀释液及其二元组合一起培养。用荧光染色后计数角蛋白阳性集落。
环巴胺浓度依赖性地抑制 HNSCC 离体生长[（IC50）约 500 nM]。在二元组合中，环巴胺可增强顺铂和多西他赛对 HNSCC 集落形成的抑制作用。
我们的研究结果定义 SMO——HH 成分之一——为 HNSCC 的潜在靶点，并提示 HH 靶向在未来 HNSCC 的多模式治疗方案中具有应用价值。
