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Updated: May 13, 2026
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
CDK2 knockdown enhances head and neck cancer cell radiosensitivity
Ahmed Soffar1, Katja Storch, Eiman Aleem
1OncoRay - National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, 01307 Dresden, Germany.
Purpose:
Cyclin-dependent kinase 2 (CDK2) is critically involved in cell cycling and has been proposed as a potential cancer target. It remains largely elusive whether CDK2 targeting alters the tumor cell radiosensitivity.
Materials And Methods:
CDK2(-/-) and wild type (WT) mouse embryonic fibroblasts (MEF) as well as six human head and neck squamous cell carcinoma (HNSCC) cell lines (SAS, FaDu, Cal-33, HSC-4, UTSCC-5, UTSCC-8) were used. Upon CDK2 knockdown using small interfering technology, colony formation, DNA double-strand breaks (DSB), cell cycle distribution and expression and phosphorylation of major proteins regulating cell cycle and DNA damage repair were examined.
Results:
CDK2(-/-) MEF and CDK2 HNSCC knockdown cell cultures were more radiosensitive than the corresponding controls. Repair of DSB was attenuated under CDK2 knockout or knockdown. In contrast to data in MEF, combined CDK2 knockdown with irradiation showed no cell cycling alterations in SAS and FaDu cultures. Importantly, CDK2 knockdown failed to radiosensitize SAS and FaDu when cultured in a more physiological three-dimensional (3D) extracellular matrix environment.
Conclusions:
Our findings suggest that targeting of CDK2 radiosensitizes HNSCC cells growing as monolayer. Additional studies performed under more physiological conditions are warranted to clarify the potential of CDK2 as target in radiotherapy.
Insights
Targeting cyclin-dependent kinase 2 (CDK2) increases radiosensitivity in head and neck squamous cell carcinoma (HNSCC) cells grown in 2D cultures. However, this effect is lost in 3D environments, suggesting further research is needed for radiotherapy applications.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy Research
Background:
- Cyclin-dependent kinase 2 (CDK2) plays a key role in cell cycle regulation.
- CDK2 is a potential therapeutic target in cancer treatment.
- The impact of CDK2 targeting on tumor cell radiosensitivity remains unclear.
Purpose of the Study:
- To investigate the effect of CDK2 targeting on the radiosensitivity of human head and neck squamous cell carcinoma (HNSCC) cells.
- To determine if CDK2 inhibition alters DNA damage repair and cell cycle progression following irradiation.
Main Methods:
- Utilized CDK2 knockout (CDK2(-/-)) and wild-type (WT) mouse embryonic fibroblasts (MEF).
- Employed small interfering RNA (siRNA) for CDK2 knockdown in six HNSCC cell lines.
- Assessed colony formation, DNA double-strand breaks (DSB), cell cycle distribution, and protein expression/phosphorylation.
Main Results:
- CDK2(-/-) MEF and CDK2-knockdown HNSCC cells exhibited increased radiosensitivity compared to controls.
- CDK2 targeting attenuated the repair of DNA double-strand breaks (DSB).
- CDK2 knockdown did not alter cell cycling in irradiated SAS and FaDu cells and failed to enhance radiosensitivity in a 3D extracellular matrix model.
Conclusions:
- Targeting CDK2 demonstrates radiosensitizing effects on HNSCC cells cultured as monolayers.
- Further investigation under more physiologically relevant conditions is necessary to evaluate CDK2 as a radiotherapy target.
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