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.
BACKGROUND: The hedgehog signaling pathway (HH) is involved in tumorigenesis in a variety of humanmalignancies. 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.
Entities:
Keywords:
Head and neck squamous cell carcinoma (HNSCC); cisplatin; cyclopamine; docetaxel; hedgehog pathway; synergism
Authors: Michael Berszin; Ioannis Michaelides; Julia Siemert; Louisa Röhl; Jana Wellhausen; Theresa Wald; Christopher Bohr; Julian Künzel; Tanja Gradistanac; Andreas Dietz; Veit Zebralla; Markus Pirlich; Susanne Wiegand; Gunnar Wichmann Journal: Front Oncol Date: 2022-02-28 Impact factor: 6.244
Authors: Abu Shadat M Noman; Rashed R Parag; Muhammad I Rashid; Mohammad Z Rahman; Ali A Chowdhury; Afrin Sultana; Chandsultana Jerin; Ayesha Siddiqua; Lutfur Rahman; Afsana Shirin; Junayed Nayeem; Reaz Mahmud; Sonam Akther; Rajib K Shil; Ikram Hossain; Sharmin Alam; Arfina Chowdhury; Shabnam B Basher; Abul Hasan; Shammy Bithy; Jannatul Aklima; Mizanur Rahman; Nabila Chowdhury; Tahmina Banu; Bedri Karakas; Herman Yeger; Walid A Farhat; Syed S Islam Journal: Ther Adv Med Oncol Date: 2020-03-13 Impact factor: 8.168