The mechanism of PDA/PEI/5-Fu coated esophageal stent material on inhibiting cancer associated pathological cells.

Abstract

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.