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

Abstract

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. Aspecifically designed recombinant FOXP3 shRNA plasmid was synthesized to target the human FOXP3 gene, and the plasmid was transfected into TE12 cells using aliposome 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 atumorigenesis assay in nude mice. Silencing the FOXP3 gene in the TE12 cell line (shFOXP3 group) resulted in asignificant 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 asignificant reduction in tumor volume and lung metastasis rate following cetuximab treatment (p = 0.028 and 0.007, respectively). 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.