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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
Linifanib (ABT-869) enhances radiosensitivity of head and neck squamous cell carcinoma cells
Heng-Wei Hsu1, Daila S Gridley, Paul D Kim
1Department of Pharmacology, Loma Linda University, Loma Linda, CA, USA.
Objectives:
Novel targeted therapeutic strategies to overcome radio-resistance of cancer cells traditionally treated with radiation may improve patient survival with the added benefit of reduced systemic toxicity. Herein, we tested the feasibility of Linifanib (ABT-869), a multi-receptor tyrosine kinase inhibitor of members of vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) receptor families, on radio-sensitization of Head and Neck Squamous Cell Carcinoma (HNSCC).
Materials And Methods:
UMSCC-22A and UMSCC-22B cells were treated with Linifanib and γ-radiation response was determined. Cell viability, cytotoxicity, apoptosis induction and cell cycle distribution were examined by MTT assay, colony formation assay and flow cytometry. In addition, expression of STAT3 and downstream signaling proteins were assessed using western immunoblotting.
Results:
Treatment with Linifanib resulted in cell growth inhibition, G2/M cell cycle arrest, induction of cell death via apoptosis, reduced phosphorylation of STAT3, which has been linked to radio-resistance, lower expression of cyclin D1, survivin and increased PARP cleavage. In addition, Linifanib overcame the radio-resistance of the cell lines and significantly enhanced radiation-induced cytotoxicity (p<0.05).
Conclusion:
These data suggest the possibility of combining targeted therapeutic such as Linifanib with radiation to enhance inhibition of cell growth and apoptosis in HNSCC cells. Thus, it may provide a novel therapeutic strategy and improve efficacy of radiation against HNSCC in the future.
Insights
Linifanib, a targeted therapy, overcomes radio-resistance in Head and Neck Squamous Cell Carcinoma (HNSCC) by inhibiting STAT3 signaling. Combining Linifanib with radiation enhances cancer cell death, offering a novel therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy
Background:
- Radio-resistance in Head and Neck Squamous Cell Carcinoma (HNSCC) limits treatment efficacy.
- Targeted therapies offer potential to overcome radio-resistance and reduce toxicity.
Purpose of the Study:
- To evaluate Linifanib's efficacy in radio-sensitizing HNSCC cells.
- To investigate the molecular mechanisms underlying Linifanib's effect on radio-resistance.
Main Methods:
- UMSCC-22A and UMSCC-22B cells were treated with Linifanib and gamma radiation.
- Assays included MTT, colony formation, flow cytometry, and western immunoblotting for cell viability, apoptosis, cell cycle, and protein expression (STAT3).
Main Results:
- Linifanib inhibited cell growth, induced G2/M arrest and apoptosis, and reduced STAT3 phosphorylation.
- Linifanib overcame radio-resistance and significantly enhanced radiation-induced cytotoxicity in HNSCC cells (p<0.05).
Conclusions:
- Linifanib combined with radiation enhances growth inhibition and apoptosis in HNSCC.
- This combination represents a potential novel therapeutic strategy to improve radiation efficacy against HNSCC.
