title: Correlation of Notch1 expression and activation to cisplatin-sensitivity of head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  Notch1 belongs to the Notch family of transmembrane receptors and plays an important role in tumor cell proliferation and apoptosis. Notch1 affects chemosensitivity of tumors. However, its correlation to cisplatin (DDP)-sensitivity of head and neck squamous cell carcinoma is unclear. This study was to identify the expression of Notch1 in head and neck squamous cell carcinoma, and investigate its influence on the DDP-sensitivity.
  
  
  METHODS
  Twenty-five fresh specimens of head and neck squamous cell carcinoma were subjected to primary cell culture. DDP-sensitivity of tumor cells was detected using collagen gel droplet embedded culture-drug sensitivity test (CD-DST). The expression of Notch1 in head and neck squamous cell carcinoma, normal squamous epithelium, and tongue squamous cell carcinoma Tb3.1 cells was detected by immunohistochemistry or immuocytochemistry. Tb3.1 cells were divided into four groups, and received treatment of DMSO, DAPT, DMSO plus DDP, DAPT plus DDP, respectively. The absorbance of the four groups was detected by CD-DST to evaluate DDP-sensitivity.
  
  
  RESULTS
  The positive rate of Notch1 was significantly higher in head and neck squamous cell carcinoma than in normal squamous epithelium (100% vs. 35%, p < 0.001), and it was negatively correlated to DDP-sensitivity (r = -0.705, p < 0.01). There was no difference in absorbance between DMSO group and DAPT group (155.4 +/- 2.3 vs. 154.7 +/- 1.2, p > 0.05), while the absorbance was significantly higher in DMSO plus DDP group than in DAPT plus DDP (33.9 +/- 1.3 vs. 26.6 +/- 1.1, p < 0.05).
  
  
  CONCLUSIONS
  Notch1 expression is negatively correlated to DDP-sensitivity of head and neck squamous cell carcinoma, and could be used to predict DDP-sensitivity. DAPT can enhance DDP-sensitivity of Tb3.1 cells via blocking Notch1 signaling.
authors: The First Department of Head and Neck, Tianjin Medical University, Tianjin, PR China.
authors: Zu-Ping
authors: ZP
authors: Zhang
authors: Yu-Lan
authors: YL
authors: Sun
authors: Li
authors: L
authors: Fu
authors: Feng
authors: F
authors: Gu
authors: Lun
authors: L
authors: Zhang
authors: Xi-Shan
authors: XS
authors: Hao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051881:Receptor, Notch1 / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004151:Dipeptides; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D002945:Cisplatin; D004121:Dimethyl Sulfoxide