Document Detail

Correlation of Notch1 expression and activation to cisplatin-sensitivity of head and neck squamous cell carcinoma.
MedLine Citation:
PMID:  19550121     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND 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.
Zu-Ping Zhang; Yu-Lan Sun; Li Fu; Feng Gu; Lun Zhang; Xi-Shan Hao
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-23
Journal Detail:
Title:  Ai zheng = Aizheng = Chinese journal of cancer     Volume:  28     ISSN:  1000-467X     ISO Abbreviation:  Ai Zheng     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-06-26     Completed Date:  2009-10-22     Revised Date:  2010-04-08    
Medline Journal Info:
Nlm Unique ID:  9424852     Medline TA:  Ai Zheng     Country:  United States    
Other Details:
Languages:  eng     Pagination:  100-3     Citation Subset:  IM    
The First Department of Head and Neck, Tianjin Medical University, Tianjin, PR China.
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MeSH Terms
Antineoplastic Agents / pharmacology
Carcinoma, Squamous Cell / metabolism*,  pathology
Cell Survival / drug effects
Cisplatin / pharmacology*
Dimethyl Sulfoxide / pharmacology
Dipeptides / pharmacology
Drug Screening Assays, Antitumor / methods
Epithelium / metabolism,  pathology
Head and Neck Neoplasms / metabolism*,  pathology
Receptor, Notch1 / biosynthesis*
Signal Transduction / drug effects
Tumor Cells, Cultured
Reg. No./Substance:
0/Antineoplastic Agents; 0/Dipeptides; 0/N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; 0/NOTCH1 protein, human; 0/Receptor, Notch1; 15663-27-1/Cisplatin; 67-68-5/Dimethyl Sulfoxide

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