Correlation of Notch1 expression and activation to cisplatin-sensitivity of head and neck squamous cell carcinoma.
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.
Zhang
Zu-Ping
ZP
The First Department of Head and Neck, Tianjin Medical University, Tianjin, PR China.
Sun
Yu-Lan
YL
Fu
Li
L
Gu
Feng
F
Zhang
Lun
L
Hao
Xi-Shan
XS
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
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