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Correlation of Notch1 expression and activation to cisplatin-sensitivity of head and neck squamous cell carcinoma
Zu-Ping Zhang1, Yu-Lan Sun, Li Fu
1The First Department of Head and Neck, Tianjin Medical University, Tianjin, PR China.
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.
Insights
Notch1 expression is linked to reduced cisplatin sensitivity in head and neck cancers. Blocking Notch1 with DAPT enhances cisplatin effectiveness, suggesting it can predict and improve treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Notch1 is a transmembrane receptor involved in tumor cell proliferation and apoptosis.
- Notch1 influences tumor chemosensitivity, but its role in head and neck squamous cell carcinoma (HNSCC) cisplatin sensitivity is not well understood.
Purpose of the Study:
- To determine Notch1 expression levels in HNSCC.
- To investigate the impact of Notch1 on cisplatin (DDP) sensitivity in HNSCC.
Main Methods:
- Primary cell cultures from 25 HNSCC specimens.
- Collagen gel droplet embedded culture-drug sensitivity test (CD-DST) to assess DDP sensitivity.
- Immunohistochemistry/immuocytochemistry to detect Notch1 expression.
- Treatment of HNSCC cell line (Tb3.1) with DMSO, DAPT (Notch inhibitor), DDP, or DAPT + DDP.
Main Results:
- Notch1 expression was significantly higher in HNSCC (100%) compared to normal squamous epithelium (35%).
- Notch1 expression showed a negative correlation with DDP sensitivity (r = -0.705).
- DAPT treatment enhanced DDP sensitivity in Tb3.1 cells, indicated by lower absorbance post-treatment compared to DDP alone.
Conclusions:
- Notch1 expression is inversely correlated with DDP sensitivity in HNSCC.
- Notch1 can serve as a predictive marker for DDP sensitivity in HNSCC.
- DAPT enhances DDP sensitivity in HNSCC cells by inhibiting Notch1 signaling.
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