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Updated: Oct 22, 2025

Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Stimulator of interferon response cGAMP interactor overcomes ERBB2-mediated apatinib resistance in head and neck
Guo Ye1,2, Junbin Zhang1,2, Chengyao Zhang1,2
1Department of Head and Neck Cancer Center, Chongqing University Cancer Hospital, Chongqing 400030, China.
Purpose:
Apatinib resistance is the main obstacle to the effective treatment of advanced head and neck squamous cell carcinoma (HNSCC). This study aimed to evaluate the function of Erb-B2 receptor tyrosine kinase 2 (ERBB2) and stimulator of interferon response cGAMP interactor (STING) in apatinib resistance in HNSCC.
Method:
The Cancer Genome Atlas database of HNSCC was used to analyze the relationship between vascular endothelial growth factor receptor 2 (VEGFR2) expression and prognosis. An apatinib resistant (AR) HNSCC cell line was constructed based on the CAL27 cell line. RNA sequencing was performed to explore the differentially expressed mRNAs. Quantitative real-time reverse transcription PCR (qRT-PCR) and western blotting were used to evaluate the expression and phosphorylation level VEGFR2, ERBB2, STING, and related proteins. Apatinib resistance was evaluated by colony formation and cell viability assays. A mouse subcutaneous tumor formation model was established to evaluate the efficiency of combination treatment and vascularization was evaluated by assessing CD31 immunofluorescence.
Result:
The expression of VEGFR2 was high in tumor of patients with HNSCC. Western blotting and qRT-PCR revealed that in AR cells, ERBB2 expression was high, whereas the expression of STING was low. Targeted treatment of ERBB2 using lapatinib could attenuate apatinib resistance. Further research confirmed that overexpressing STING could decrease ERBB2 expression.
Conclusion:
STING could sensitize AR cells to apatinib by decreasing ERBB2 expression. The combination of lapatinib or a STING agonist with apatinib ameliorated acquired apatinib resistance in a synergistic manner.
Insights
Stimulator of interferon response cGAMP interactor (STING) can overcome apatinib resistance in head and neck squamous cell carcinoma (HNSCC) by reducing Erb-B2 receptor tyrosine kinase 2 (ERBB2) expression. Combining STING agonists or lapatinib with apatinib offers a synergistic approach to treating HNSCC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Apatinib resistance presents a significant challenge in treating advanced head and neck squamous cell carcinoma (HNSCC).
- Understanding the molecular mechanisms underlying apatinib resistance is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the roles of Erb-B2 receptor tyrosine kinase 2 (ERBB2) and stimulator of interferon response cGAMP interactor (STING) in the development of apatinib resistance in HNSCC.
- To explore potential therapeutic strategies to overcome apatinib resistance by targeting ERBB2 and STING pathways.
Main Methods:
- Analysis of The Cancer Genome Atlas database for HNSCC patient data.
- Construction of an apatinib-resistant (AR) HNSCC cell line and subsequent RNA sequencing.
- Quantitative real-time reverse transcription PCR (qRT-PCR) and western blotting to assess protein expression and phosphorylation.
- In vitro assays (colony formation, cell viability) and in vivo mouse models to evaluate treatment efficacy and vascularization.
Main Results:
- Elevated vascular endothelial growth factor receptor 2 (VEGFR2) expression was observed in HNSCC tumors.
- Apatinib-resistant HNSCC cells exhibited high ERBB2 expression and low STING expression.
- Targeting ERBB2 with lapatinib reduced apatinib resistance, while STING overexpression decreased ERBB2 levels.
Conclusions:
- STING sensitizes apatinib-resistant HNSCC cells to apatinib by downregulating ERBB2 expression.
- Combination therapy involving lapatinib or a STING agonist with apatinib demonstrated synergistic effects in overcoming acquired apatinib resistance.
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