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Updated: Nov 11, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Simvastatin inhibits oral squamous cell carcinoma by targeting TMEM16A Ca2+-activated chloride channel
Hechen Wang1,2, Tianyu Wang2, Zeying Zhang1
1Liaoning Provincial Key Laboratory of Oral Diseases, Department of Oromaxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, 117 Nanjing Bei Jie, Heping District, Shenyang,, 110002, Liaoning, China.
Purpose:
Ca2+-activated chloride channel TMEM16A has been found to be overexpressed in many cancers including head and neck squamous cell carcinoma (HNSCC). Nevertheless, the role of TMEM16A in oral squamous cell carcinoma (OSCC) remains unclear. Although simvastatin is known to produce anti-tumor effect, the mechanisms by which simvastatin inhibits cancer remain unclear.
Methods:
In this study, we explored the role of TMEM16A expression in human OSCC tissues using both TCGA dataset and immunohistochemistry. CCK-8 assay was applied to evaluate cell proliferation. Patch clamp technique was applied to record TMEM16A Cl- currents.
Results:
We found that high TMEM16A expression is related with large tumor size, lymph node metastasis, and poor clinical outcome in patients with OSCC. In addition, TMEM16A overexpression could promote cell proliferation, and inhibition of TMEM16A channel activities could suppress cell proliferation in OSCC cells. Furthermore, simvastatin could suppress TMEM16A channel activities, and inhibited cell proliferation in OSCC cells via TMEM16A.
Conclusion:
Our findings identify a novel anti-tumor mechanism of simvastatin by targeting TMEM16A. Simvastatin may represent an innovative strategy for treating OSCC with high TMEM16A expression.
Insights
High TMEM16A expression correlates with poor outcomes in oral squamous cell carcinoma (OSCC). Simvastatin inhibits OSCC cell proliferation by targeting TMEM16A, offering a potential new treatment strategy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Calcium-activated chloride channel TMEM16A is overexpressed in various cancers, including head and neck squamous cell carcinoma (HNSCC).
- The specific role of TMEM16A in oral squamous cell carcinoma (OSCC) and the anti-tumor mechanisms of simvastatin are not fully understood.
Purpose of the Study:
- To investigate the role of TMEM16A expression in OSCC.
- To explore the anti-tumor effects of simvastatin on OSCC cells by targeting TMEM16A.
Main Methods:
- Analysis of TMEM16A expression in human OSCC tissues using TCGA dataset and immunohistochemistry.
- Cell proliferation assessed via CCK-8 assay.
- TMEM16A chloride currents recorded using patch clamp technique.
Main Results:
- High TMEM16A expression is associated with larger tumor size, lymph node metastasis, and poorer clinical outcomes in OSCC patients.
- TMEM16A overexpression promotes OSCC cell proliferation; inhibiting TMEM16A suppresses proliferation.
- Simvastatin inhibits TMEM16A channel activity and suppresses OSCC cell proliferation.
Conclusions:
- Simvastatin exhibits anti-tumor effects in OSCC by targeting TMEM16A.
- Targeting TMEM16A with simvastatin presents a potential novel therapeutic strategy for OSCC patients with high TMEM16A expression.
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