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Wiener klinische Wochenschrift

24.10.2023 | original article

FOXP3 expression in esophageal squamous cell carcinoma

Implications for cetuximab sensitivity and therapeutic strategies

verfasst von: Shenghong Wu, Yu Wang, Zhijun Xiao, Jinfeng Zhang, Zhonghui He, Ming Ye

Erschienen in: Wiener klinische Wochenschrift

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Summary

Objective

Investigating the impact of FOXP3 (transcription factor forkhead box P3) expression on the biological behavior of esophageal squamous cell carcinoma (ESCC) and its influence on the sensitivity of ESCC cells towards cetuximab-targeted (an EGFR monoclonal antibody inhibitor) therapy.

Methods

A specifically designed recombinant FOXP3 shRNA plasmid was synthesized to target the human FOXP3 gene, and the plasmid was transfected into TE12 cells using a liposome method. Multiple assays were conducted to evaluate the effect of FOXP3 expression on ESCC cells and their response to cetuximab treatment. Proliferation activity and cetuximab sensitivity of ESCC cells were measured using the CCK‑8 assay. The invasion ability of cells was assessed using an in vitro invasion assay. Furthermore, the efficacy of cetuximab in treating ESCC was analyzed using a tumorigenesis assay in nude mice.

Results

Silencing the FOXP3 gene in the TE12 cell line (shFOXP3 group) resulted in a significant reduction in FOXP3 mRNA and protein expression (p = 0.013). The shFOXP3 group exhibited slowed cell growth (p = 0.035), decreased invasion rate (p = 0.031), and increased sensitivity to cetuximab treatment (p = 0.039) compared to the control group (shNC group). In the in vivo tumorigenesis assay, the shFOXP3 group demonstrated a significant reduction in tumor volume and lung metastasis rate following cetuximab treatment (p = 0.028 and 0.007, respectively).

Conclusion

High FOXP3 expression promotes the proliferation and migration of ESCC cells, while negatively affecting their sensitivity to cetuximab-targeted therapy. Consequently, targeting FOXP3 shows potential therapeutic implications for enhancing the effectiveness of cetuximab treatment in ESCC patients.

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Titel: FOXP3 expression in esophageal squamous cell carcinoma
Implications for cetuximab sensitivity and therapeutic strategies
verfasst von: Shenghong Wu
Yu Wang
Zhijun Xiao
Jinfeng Zhang
Zhonghui He
Ming Ye
Publikationsdatum: 24.10.2023
Verlag: Springer Vienna
Erschienen in: Wiener klinische Wochenschrift
Print ISSN: 0043-5325
Elektronische ISSN: 1613-7671
DOI: https://doi.org/10.1007/s00508-023-02291-4