TY - JOUR T1 - Hedgehog Targeting by Cyclopamine Suppresses Head and Neck Squamous Cell Carcinoma and Enhances Chemotherapeutic Effects JF - Anticancer Research JO - Anticancer Res SP - 2415 LP - 2424 VL - 33 IS - 6 AU - CHRISTIAN MOZET AU - MATTHAEUS STOEHR AU - KAMELIA DIMITROVA AU - ANDREAS DIETZ AU - GUNNAR WICHMANN Y1 - 2013/06/01 UR - http://ar.iiarjournals.org/content/33/6/2415.abstract N2 - Background: 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. Patients and Methods: 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. Results: 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. Conclusion: 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. ER -