Department of Medical Oncology, Fengxian District Central Hospital, 201499, Shanghai, China.
Department of Oncology, Huashan Hospital, Fudan University, 200040, Shanghai, China.
Wien Klin Wochenschr. 2024 Jun;136(11-12):331-339. doi: 10.1007/s00508-023-02291-4. Epub 2023 Oct 24.
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.
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.
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).
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.
研究叉头框蛋白 P3（FOXP3）表达对食管鳞状细胞癌（ESCC）生物学行为的影响及其对 ESCC 细胞对西妥昔单抗靶向（EGFR 单克隆抗体抑制剂）治疗敏感性的影响。
设计了一种特异性靶向人 FOXP3 基因的重组 FOXP3 shRNA 质粒，并用脂质体法转染 TE12 细胞。通过多种实验评估 FOXP3 表达对 ESCC 细胞及其对西妥昔单抗治疗反应的影响。使用 CCK-8 法检测 ESCC 细胞的增殖活性和西妥昔单抗敏感性。通过体外侵袭实验评估细胞的侵袭能力。此外，还在裸鼠肿瘤发生模型中分析了西妥昔单抗治疗 ESCC 的疗效。
沉默 TE12 细胞系中的 FOXP3 基因（shFOXP3 组）导致 FOXP3 mRNA 和蛋白表达显著降低（p=0.013）。与对照组（shNC 组）相比，shFOXP3 组细胞生长速度减慢（p=0.035），侵袭率降低（p=0.031），对西妥昔单抗治疗的敏感性增加（p=0.039）。在体内肿瘤发生实验中，shFOXP3 组在西妥昔单抗治疗后肿瘤体积和肺转移率显著降低（p=0.028 和 0.007）。
高 FOXP3 表达促进 ESCC 细胞的增殖和迁移，同时降低其对西妥昔单抗靶向治疗的敏感性。因此，靶向 FOXP3 可能为增强 ESCC 患者西妥昔单抗治疗的效果提供潜在的治疗意义。
