Metal stent implantation is usually applied to alleviate nonoperative palliative esophageal obstruction for esophageal cancer in the later period. However, in‐stent restenosis after stent implantation limits the esophageal stents' performance due to lack of effective suppression of pathological cells from cancer microenvironment. In previous work, we modified the esophageal stent material 317L stainless steel (317LSS) surface with a poly‐dopamine/poly‐ethylenimine/5‐fluorouracil layer (PDA/PEI/5‐Fu), which had strong anti‐tumor and anti‐restenosis functions. Nevertheless, the mechanism of PDA/PEI/5‐Fu layer against tumor and inflammation remains unclear. In this work, we revealed the mechanism of PDA/PEI/5‐Fu suppressing the esophageal cancer related pathological cells (esophageal tumor cells, epithelial cells, and fibroblast) and inflammatory cells (macrophages) via series of experiments. Our data suggested that the PEI inhibited viability and E‐cadherin expression of the pathological cells, and blocked the NF‐κB signal pathway (reducing levels of p‐NF‐κB proteins). The loaded 5‐Fu inhibited the inflammatory factors (TNF‐α and IL‐1β) release and promoted the anti‐inflammation/anti‐tumor factors (IL‐10 and IL‐4) release from macrophages, and also suppressed pathological cells migration; both the PEI and 5‐Fu contributed to the upregulation of Bax and Caspase‐3 (pro‐tumor‐apoptosis factor), as well as the downregulation of Bcl‐2 (anti‐tumor‐apoptosis factor) in esophageal tumor cells. All the results showed that PDA/PEI/5‐Fu coating had potential multipath anti‐cancer and anti‐inflammatory effects in the surface modification of esophageal stents.

中文翻译：

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PDA/PEI/5-Fu涂层食管支架材料抑制癌相关病理细胞的作用机制

金属支架植入术常用于缓解食管癌晚期非手术姑息性食管梗阻。然而，支架植入后的支架内再狭窄由于缺乏对来自癌症微环境的病理细胞的有效抑制而限制了食管支架的性能。在以前的工作中，我们用聚多巴胺/聚乙烯亚胺/5-氟尿嘧啶层（PDA/PEI/5-Fu）对食管支架材料 317L 不锈钢（317LSS）表面进行了修饰，具有很强的抗肿瘤和抗肿瘤能力。再狭窄功能。然而，PDA/PEI/5-Fu 层抗肿瘤和炎症的机制仍不清楚。在这项工作中，我们揭示了 PDA/PEI/5-Fu 抑制食管癌相关病理细胞（食管肿瘤细胞、上皮细胞、和成纤维细胞）和炎症细胞（巨噬细胞）通过一系列实验。我们的数据表明 PEI 抑​​制了病理细胞的活力和 E-cadherin 表达，并阻断了 NF-κB 信号通路（降低 p-NF-κB 蛋白的水平）。负载的5-Fu抑制炎症因子（TNF-α和IL-1β）的释放，促进巨噬细胞释放抗炎/抗肿瘤因子（IL-10和IL-4），并抑制病理细胞迁移；PEI 和 5-Fu 都有助于食管肿瘤细胞中 Bax 和 Caspase-3（促肿瘤凋亡因子）的上调以及 Bcl-2（抗肿瘤凋亡因子）的下调。所有结果表明，PDA/PEI/5-Fu涂层在食管支架表面改性中具有潜在的多路径抗癌和抗炎作用。