中国普通外科杂志2026，Vol.35Issue(4)：830-840,11.DOI:10.7659/j.issn.1005-6947.250263
姜黄素/明胶纳米纤维膜抑制胃癌的作用研究
Inhibitory effect of curcumin/gelatin nanofibrous membrane on gastric cancer
摘要
Abstract
Background and Aims:Curcumin is a safe and inexpensive natural compound,but its clinical application in gastric cancer therapy is severely limited by poor water solubility and low bioavailability.This study aims to construct an implantable curcumin/gelatin nanofibrous membrane for local sustained drug release and to investigate its molecular mechanisms in inhibiting GC cell proliferation. Methods:Curcumin/gelatin nanofibrous membranes were prepared by electrospinning.Morphology was observed by scanning electron microscopy,and the in vitro drug release profile was determined by high-performance liquid chromatography-tandem mass spectrometry.Biocompatibility was evaluated using human gastric mucosal cells GES-1.Human gastric cancer cell lines MKN-45,SGC-7901,and AGS were treated with conditioned media from the nanofibrous membranes.Colony formation assay,reactive oxygen species(ROS)detection,and Western blot were performed to assess cell proliferation,ROS levels,and the expression of endoplasmic reticulum stress pathway proteins(BiP/p-PERK/p-eIF2α)and phosphorylated STAT3.A subcutaneous xenograft model in nude mice was established,and the membrane was placed locally on the tumor surface to evaluate in vivo anti-tumor efficacy.Immunohistochemistry was used to detect the expression of BrdU,BiP,and p-STAT3 in tumor tissues. Results:The prepared nanofibrous membrane had a smooth surface with amorphous and uniform dispersion of curcumin.In vitro release lasted for over 120 h.The material showed no obvious toxicity to normal GES-1 cells(P>0.05).It significantly inhibited colony formation of MKN-45,SGC-7901,and AGS cells(inhibition rate 60%).Mechanistically,treatment with curcumin/gelatin nanofibrous membrane significantly increased intracellular ROS levels,upregulated the expression of BiP,p-PERK,p-eIF2α,and cleaved caspase-3,and downregulated p-STAT3.At the same time,these changes were reversed by the ROS scavenger NAC(all P<0.05).In vivo,local application of the membrane significantly suppressed xenograft tumor growth,reduced tumor volume,decreased BrdU-positive cells(all P<0.05),increased BiP expression,and lowered p-STAT3 levels. Conclusion:The curcumin/gelatin nanofibrous membrane significantly enhances the bioavailability of curcumin through localized sustained release.It effectively inhibits the proliferation of gastric cancer cells and promotes their apoptosis by inducing ROS generation,activating endoplasmic reticulum stress,and suppressing STAT3 phosphorylation.With favorable biocompatibility,simple preparation,and low cost,this material shows promise as a novel and safe formulation for postoperative local adjuvant therapy of gastric cancer.关键词
胃肿瘤/姜黄素/纳米纤维膜/生物利用度/肿瘤抑制Key words
Stomach Neoplasms/Curcumin/Nanofibrous Membrane/Biological Availability/Tumor Suppressor分类
医药卫生引用本文复制引用
周晓华,徐豪,濮阳永强,芮鸿庆,王礽,孔荷香,张晶,赵华头..姜黄素/明胶纳米纤维膜抑制胃癌的作用研究[J].中国普通外科杂志,2026,35(4):830-840,11.基金项目
江苏大学临床医学科技发展基金资助项目(JLY2021176). （JLY2021176）
