现代中西医结合杂志2025，Vol.34Issue(8)：1023-1028,1056,7.DOI:10.3969/j.issn.1008-8849.2025.08.001
槐耳多糖通过p53/sLC7A11/GPX4信号轴促进三阴乳腺癌细胞铁死亡的机制研究
Mechanism of Huaier polysaccharide promoting ferroptosis in triple-negative breast cancer cells via the p53/sLC7A11/GPX4 signaling axis
摘要
Abstract
Objective It is to investigate the effect and mechanism of Huaier polysaccharides in inducing ferroptosis in triple-negative breast cancer MDA-MB-231 cells.Methods Triple-negative breast cancer MDA-MB-231 cells were treated with different concentrations of Huaier polysaccharides(0,2,4,8,16,32,64,128 μmol/L),and the cell viability was assessed by CCK-8 assay.The cells in logarithmic growth phase were randomly divided into 6 groups:control group cul-tured normally,Huaier polysaccharide group cultured with 32 μg/mL Huaier polysaccharide,Huaier polysaccharide+iron inducer group culured with 32 μg/mL Huaier polysaccharide+2 μg/mL iron inducer,iron inducer group culured with 2 μg/mL iron inducer,paclitaxel group cultured with 2.5 μmol/mL paclitaxel,and paclitaxel+Huaier polysaccharide group cultured with 2.5 μmol/mL paclitaxel+32 μg/mL Huaier polysaccharide.After 24 h of culture,the apoptosis rate and content of reactive oxygen species(ROS)in the cells were determined by flow cytometry,and the expressions of iron death-related protein tumor protein 53(p53),solute carrier family 7 member 11(sLC7A11),glutathione peroxidase 4(GPX4),trans-ferrin receptor 1(TFR1),divalent metal transporter protein 1(DMT1)were detected by Western blot.Results When the concentration of Huaier polysaccharide was more than 4 μg/mL,the survival rate of breast cancer cells gradually decreased with the increase of Huaier polysaccharide concentration,and the differences were statistically significant compared with the control group(all P<0.05),and the inhibitory effect was significant at32 μg/mL.Compared with the control group,the apoptosis rate,ROS content and relative expressions of p53,TFR1 and DMT1 proteins in cells were significantly higher,while the relative expressions of sLC7A11 and GPX4 proteins in cells were significantly lower in each medicated group(all P<0.05);the apoptosis rate,ROS content and relative expressions of p53,TFR1 and DMT1 proteins in cells of the Hua-ier polysaccharide+iron inducer group and paclitaxel+Huaier polysaccharide group were significantly higher,while the relative expressions of sLC7A11 and GPX4 proteins in cells were significantly lower than those of the Huaier polysaccharide group(all P<0.05);the apoptosis rate,ROS content and relative expressions of p53,TFR1 and DMT1 proteins in cells of the paclitaxel+Huaier polysaccharide group were significantly higher,while the relative expressions of sLC7A11 and GPX4 proteins in cells were significantly lower than those in cells of the paclitaxel group(all P<0.05).Conclusion Hua-ier polysaccharide can inhibit the proliferation of triple-negative breast cancer MDA-MB-231 cells and induce ferroptosis,the inhibition is more significant when combined with paclitaxel,the mechanism may be related to regulate p53/SLC7A11/GPX4 signaling axis.关键词
槐耳多糖/三阴乳腺癌/铁死亡/紫杉醇/肿瘤蛋白53/溶质载体家族7 成员11/谷胱甘肽过氧化物酶4Key words
Huaier polysaccharides/triple-negative breast cancer/ferroptosis/paclitaxel/p53/sLC7A11/GPX4分类
医药卫生引用本文复制引用
王玲,史晓光,高爽,汪唐顺,冯雪,王玉坤,孙萍,左禧萌,高翔..槐耳多糖通过p53/sLC7A11/GPX4信号轴促进三阴乳腺癌细胞铁死亡的机制研究[J].现代中西医结合杂志,2025,34(8):1023-1028,1056,7.基金项目
国家自然科学基金青年科学基金项目(81603583) （81603583）
湖北陈孝平科技发展基金会专项基金项目(CX-PJJH12000002-2020010) （CX-PJJH12000002-2020010）
北京中医药大学青年教师项目(2022-BUCMXJKY-009) （2022-BUCMXJKY-009）
北京中医药大学东直门医院横向课题(YX-2022-006) （YX-2022-006）
