SDC2表达调控铁死亡参与宫颈癌发生的作用及机制  

Study on the role and mechanism of SDC2 expression in regulating ferroptosis and cervical cancer

作　　者：姚雪芹[1] 肖雪莲[1] 罗其英 常德萍[1] 高燕[1] Yao Xueqin;Xiao Xuelian;Luo Qiying;Chang Deping;Gao Yan(Dept of Gynecology,Guizhou Provincial People′s Hospital,Guiyang 550002)

机构地区：[1]贵州省人民医院妇科,贵阳550002

出　　处：《安徽医科大学学报》2025年第2期234-239,共6页Acta Universitatis Medicinalis Anhui

基　　金：贵州省卫生健康科研基金项目(编号:GZ20HDF154)。

摘　　要：目的探究黏结蛋白聚糖2(SDC2)是否可通过调控铁死亡影响宫颈癌细胞增殖、侵袭、迁移及其可能的作用机制。方法培养正常宫颈上皮细胞H8、宫颈鳞状癌细胞C33A,分为H8组与C33A组。培养C33A细胞,分为对照组、低表达SDC2组、低表达SDC2+铁死亡抑制剂(ferrostation-1)组与低表达SDC2+铁死亡诱导剂(erastin)组。Western blot检测细胞中SDC2、溶质载体家族7成员11(SLC7A11)、谷胱甘肽过氧化酶4(GPX4)蛋白。RT-qPCR检测C33A细胞中SDC2 mRNA水平。ELISA试剂盒检测C33A细胞中活性氧(ROS)、谷胱甘肽(GSH)、亚铁离子(Fe^(2+))水平。平板克隆检测C33A细胞克隆能力。划痕实验检测C33A细胞迁移能力。Transwell实验检测C33A细胞侵袭能力。结果与H8组比较,C33A组细胞中SDC2、SLC7A11、GPX4蛋白及mRNA表达增加(P<0.05)。与对照组比较,低表达SDC2组C33A细胞增殖、迁移及侵袭能力降低(P<0.05),C33A细胞中SLC7A11、GPX4蛋白及mRNA表达减少(P<0.05),GSH水平减少,ROS及Fe^(2+)水平增加(P<0.05)。与低表达SDC2组比较,低表达SDC2+ferrostation-1组SLC7A11、GPX4蛋白及mRNA表达增加(P<0.05),GSH水平增加,ROS及Fe^(2+)水平减少(P<0.05)。与对照组比较,低表达SDC2+erastin组C33A细胞增殖、迁移及侵袭能力降低(P<0.05)。结论SDC2在C33A宫颈癌细胞中表达增加,低表达SDC2可激活SLC7A11/GPX4通路介导的铁死亡,从而降低C33A细胞的增殖、侵袭及迁移能力。Objective To investigate whether syndecan-2(SDC2)can affect the proliferation,invasion and migration of cervical cancer cells by regulating ferroptosis and its possible mechanism.Methods Normal cervical epithelial cells H8 and cervical squamous carcinoma cells C33A were cultured and divided into H8 group and C33A group.C33A cells were cultured and divided into control group,low SDC2 expression group,SDC2+ferroptosis inhibitor(ferrostation-1)group and SDC2+ferroptosis inducer(erastin)group.Western blot was used to detect the protein levels of SDC2,solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4).RT-qPCR was used to detect the SDC2 mRNA level in C33A cells.ELISA kits were used to detect the levels of reactive oxygen species(ROS),glutathione(GSH)and ferrous ion(Fe^(2+))in C33A cells.The cloning ability of C33A cells was detected by plate cloning.The migration ability of C33A cells was detected by scratch test.Transwell assay was used to detect the invasion ability of C33A cells.Results Compared with H8 group,the protein and mRNA expressions of SDC2,SLC7A11 and GPX4 in C33A group increased(P<0.05).Compared with the control group,the proliferation ability,migration ability and invasion ability of C33A cells in the low SDC2 group decreased(P<0.05),the protein and mRNA expressions of SLC7A11 and GPX4 in C33A cells decreased(P<0.05),and the GSH level decreased.ROS and Fe^(2+)levels increased(P<0.05).Compared with the low SDC2 group,the protein and mRNA expressions of SLC7A11 and GPX4 increased(P<0.05),the GSH level increased,and the ROS and Fe^(2+)levels decreased(P<0.05)in the low SDC2+ferrostation-1 group.Compared with the control group,the proliferation ability,migration ability and invasion ability of C33A cells with low SDC2+erastin expression decreased(P<0.05).Conclusion The expression of SDC2 increases in C33A cervical cancer cells.Low expression of SDC2 can activate SLC7A11/GPX4 pathway mediated ferroptosis,thereby reducing the proliferation,invasion and migration of C33A cells.

关 键 词：宫颈癌 SDC2 铁死亡 增殖 迁移 侵袭 

分 类 号：R737.33[医药卫生—肿瘤]