槐耳多糖诱导三阴性乳腺癌MDA-MB-231细胞铁死亡的作用机制*

作者：王 玲，高 翔，高 爽，汪唐顺，冯 雪，王玉坤，孙 萍，左禧萌，史晓光

单位：北京中医药大学东直门医院，北京 100700

引用：引用：王玲，高翔，高爽，汪唐顺，冯雪，王玉坤，孙萍，左禧萌，史晓光.槐耳多糖诱导三阴性乳腺癌MDA-MB-231细胞铁死亡的作用机制[J].中医药导报,2025,31(8):47-52.

DOI：10.13862/j.cn43-1446/r.2025.08.008

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摘要：目的：探讨槐耳多糖诱导三阴性乳腺癌MDA-MB-231细胞铁死亡的作用机制。方法：通过CCK-8实验检测槐耳多糖不同浓度、不同干预时间对MDA-MB-231细胞活性的影响；取对数生长期的MDA-MB-231细胞，随机分成6组，分别为对照组（NC组）、槐耳多糖组（PS-T组）、槐耳多糖+铁诱导剂组（PS-T+Erastin组）、铁诱导剂组（Erastin组）、紫杉醇组（PTX组）和槐耳多糖+紫杉醇组（PS-T+PTX组），用克隆形成实验检测各组MDA-MB-231细胞的增殖情况；用铁死亡相关试剂盒检测细胞内亚铁离子（Fe2+）、谷胱甘肽（GSH）和丙二醛（MDA）的含量；通过JC-1线粒体膜电位检测试剂盒检测MDA-MB-231细胞的线粒体膜电位，并用流式细胞仪进行分析；用DCFH-DA探针对活性氧（ROS）进行检测，并用荧光显微镜进行分析；用实时定量PCR仪检测MDA-MB-231细胞内p53 mRNA、SLC7A11 mRNA、GPX4 mRNA、TFR1 mRNA和DMT1 mRNA的表达情况。结果：与NC组比较，乳腺癌细胞的活力随槐耳多糖的浓度升高而逐渐降低（P＜0.05），且24 h比48 h的作用更显著；与NC组比较，PS-T组、PS-T+Erastin组、Erastin组、PTX组和PS-T+PTX组的克隆形成率、GSH含量、线粒体膜电位以及GPX4 mRNA和SLC7A11 mRNA表达均显著下降，而Fe2+、MDA含量、ROS水平以及DMT1 mRNA、TFR1 mRNA和p53 mRNA表达则显著升高（P＜0.05）；与PS-T组比较，PS-T+Erastin组和PS-T+PTX组的克隆形成率、GSH含量、线粒体膜电位以及GPX4 mRNA和SLC7A11 mRNA表达均下调，而Fe2+、MDA含量、ROS水平以及DMT1 mRNA、TFR1 mRNA和p53 mRNA表达则上调（P＜0.05）。结论：槐耳多糖可以诱导三阴性乳腺癌MDA-MB-231细胞的铁死亡，其作用机制可能与Fe2+积累和脂质过氧化相关。

关键词：乳腺恶性肿瘤；槐耳多糖；铁死亡；线粒体膜电位；脂质过氧化

Abstract：

Objective: To investigate the mechanism of ferroptosis induced by sophora polysaccharides in triple-negative breast cancer MDA-MB-231 cells. Methods: CCK-8 assay was used to detect the effects of different concentrations and different times of polysaccharides on the activity of MDA-MB-231 cells. The MDA-MB-231 cells in logarithmic growth phase were randomly divided into 6 groups, including control group (NC group), sophora polysaccharide group (PS-T group), sophora polysaccharide + iron inducion dose group (PS-T+Erastin group), iron inducer group (Erastin group), paclitaxel group (PTX group) and sophora polysaccharide + paclitaxel group (PS-T+PTX group). The proliferation of MDA-MB-231 cells in each group was detected by clonal formation assay. The contents of ferrous ions (Fe2+), glutathione (GSH) and malondialdehyde (MDA) were detected with ferroptosis-related kits. The mitochondrial membrane potential of MDA-MB-231 cells was detected by JC-1 mitochondrial membrane potential detection kit and analyzed by flow cytometry. DCFH-DA probe was used to detect reactive oxygen (ROS), and fluorescence microscope was used for analysis. The p53 mRNA, SLC7A11 mRNA, GPX4 mRNA, TFR1 mRNA and DMT1 mRNA levels of MDA-MB-231 were detected by real-time quantitative PCR instrument. Results: Compared with NC group, the viability of breast cancer cells decreased gradually with the increase of the concentration of sophora polysaccharides (P<0.05), and the effect was more significant in 24 h than in 48 h. Compared with NC group, the clone formation rate, GSH content, mitochondrial membrane potential, GPX4 mRNA expression and SLC7A11 mRNA expression decreased in PS-T group, PS-T+Erastin group, Erastin group, PTX group and PS-T+PTX group, while Fe2+, MDA content, ROS level, DMT1 mRNA expression, TFR1 mRNA expression and p53 mRNA expression were significantly increased (P<0.05). Compared with PS-T group, the clonogenic rate, GSH content, mitochondrial membrane potential, GPX4 mRNA expressions and SLC7A11 mRNA expressions were down-regulated in PS-T+Erastin grouop and PS-T+PTX group, while Fe2+, MDA content, ROS levels,  DMT1 mRNA expression, TFR1  mRNA expression, and p53 mRNA expression were up-regulated (P<0.05). Conclusion: Sophora polysaccharides can induce ferroptosis in triple negative breast cancer MDA-MB-231 cells, and its mechanism may be related to Fe2+ accumulation and lipid peroxidation.

Key words：malignant tumors of the breast; sophora polysaccharides; ferroptosis; mitochondrial membrane potential; lipid peroxidation

发布时间：2026-01-06

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