七叶皂苷通过刺激活性氧水平激活Caspase-1/GSDMD信号通路促进乳腺癌细胞焦亡  

Escin promotes pyroptosis in breast cancer cells through ROS/Caspase-1/GSDMD signaling pathway

作　　者：丁紫琳 李晨媛 王钟 李智宇 孙圣荣[1] DING Zilin;LI Chenyuan;WANG Zhong;LI Zhiyu;SUN Shengrong(Department of Breast and Thyroid Surgery,Renmin Hospital of Hubei Province,Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院乳腺甲状腺外科,430060

出　　处：《临床外科杂志》2025年第3期284-288,共5页Journal of Clinical Surgery

基　　金：国家自然科学基金资助项目(82203374);中央高校基本科研业务费专项资金资助项目(2042023kf0020,2042022kf1081)。

摘　　要：目的探讨七叶皂苷(Escin)抑制乳腺癌(BC)细胞进展的新机制。方法设置不同浓度(0,10,20,30,40μg/ml)的Escin处理组,用对应浓度的Escin处理BC细胞,然后利用CCK8、克隆形成,流式细胞术,透射电镜观察和蛋白免疫印迹等实验方法评估细胞表型和可能机制;设置对照组、Escin组和Escin+VX-765组,利用Caspase-1抑制剂VX-765预处理细胞,确定Caspase-1/GSDMD信号通路在Escin诱导BC细胞焦亡中的作用;设置对照组、Escin组和Escin+NAC组,利用活性氧(ROS)清除剂乙酰半胱氨酸(N-Acetylcysteine,NAC)预处理细胞,确定ROS在Escin诱导BC细胞焦亡中的作用。结果与对照组比较,不同浓度Escin对BC细胞增殖及克隆形成具有抑制作用,且呈浓度依赖性(P<0.05)。Escin处理组与对照组相比ROS和焦亡率升高(P<0.05);FL-GSDMD,pro-Caspase-1蛋白表达降低,N-GSDMD,cleaved Caspase-1,IL-18蛋白表达升高(P<0.05)。与Escin组比较,Escin+VX-765组细胞增殖率升高(P<0.05),焦亡蛋白表达降低(P<0.05)。与Escin组相比,Escin+NAC组细胞增殖率升高(P<0.05),ROS、焦亡率及焦亡蛋白表达降低(P<0.05)。结论Escin抑制BC细胞生长可能与其调控ROS/Caspase-1/GSDMD信号通路促进BC细胞焦亡有关。Objective To explore the new mechanism of Escin inhibiting the progression of breast cancer cells.Methods Escin treatment groups with different concentrations(0,10,20,30,40μg/ml)were set up,and BC cells were treated with corresponding concentrations of Escin,then CCK8,clonal formation,flow cytometry,transmission electron microscopy and protein immunoblotting were used to evaluate the cell phenotype and possible mechanisms.Control group,Escin group and Escin+VX-765 group were set up,to determine the role of Caspase-1/GSDMD signaling pathway in Escin-induced pyroptosis of BC cells,cells were pretreated with Caspase-1 inhibitor VX-765.The cells in control group,Escin group and Escin+NAC group were pretreated with the reactive oxygen species(ROS)scavher N-Acetylcysteine(NAC),to determine the role of ROS in Escin induced pyroptosis of BC cells.Results Compared with the control group,different concentrations of Escin inhibited the proliferation and colony formation of BC cells in a concentration dependent manner(P<0.05).Compared with the control group,the ROS and pyroptosis rate were increased in Escin-treated group(P<0.05).The protein expression levels of FL-GSDMD and pro-Caspase-1 were significantly decreased in the Escin-treated group,while N-GSDMD,cleaved Caspase-1 and IL-18 protein expression were significantly increased(P<0.05).Compared with the Escin-treated group,the proliferation rate of Escin+VX-765 group was increased(P<0.05),and the expression of pyroptosis protein was decreased(P<0.05).Compared with the Escin-treated group,the proliferation rate of Escin+NAC group was increased(P<0.05),and the ROS,pyroptosis rate and pyroptosis protein expression were decreased(P<0.05).Conclusion The inhibitory effect of Escin on the progression of breast cancer cells may be related to its regulation of ROS/Caspase-1/GSDMD signaling pathway to promote cell pyroptosis.

关 键 词：乳腺癌 细胞焦亡 七叶皂苷 GSDMD CASPASE-1 

分 类 号：R49[医药卫生—康复医学]