• Wien. Klin. Wochenschr. · Jun 2024

    FOXP3 expression in esophageal squamous cell carcinoma : Implications for cetuximab sensitivity and therapeutic strategies.

    • Shenghong Wu, Yu Wang, Zhijun Xiao, Jinfeng Zhang, Zhonghui He, and Ming Ye.
    • Department of Medical Oncology, Fengxian District Central Hospital, 201499, Shanghai, China.
    • Wien. Klin. Wochenschr. 2024 Jun 1; 136 (11-12): 331339331-339.

    ObjectiveInvestigating 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.MethodsA 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.ResultsSilencing 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).ConclusionHigh 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.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.

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