基于蛋白质组学分析重楼皂苷I抑制食管鳞癌细胞生长的分子机制  

Molecular mechanism study on polyphyllin I inhibits the growth of esophageal squamous cell carcinoma based on proteomics

作　　者：杨艺 李姗[1] 晋果果 史文杰 刘湘花[4] 张悦 禄保平[3] YANG Yi;LI Shan;JIN Guoguo;SHI Wenjie;LIU Xianghua;ZHANG Yue;LU Baoping(School of Medicine,Henan University of Chinese Medicine,Zhengzhou 450046,China;Henan Key Laboratory of Chronic Disease Management,Fuwai Central China Cardiovascular Hospital,Zhengzhou 450046,China;The Second Clinical Medical College of Henan University of Chinese Medicine,Zhengzhou 450046,China;Academy of Chinese Medicine,Henan University of Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学医学院,郑州450046 [2]阜外华中心血管病医院慢病健康管理重点实验室,郑州450046 [3]河南中医药大学第二临床医学院,郑州450046 [4]河南中医药大学中医药研究院,郑州450046

出　　处：《中华中医药杂志》2025年第3期1411-1415,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：河南中医药大学优秀博士科研启动金(No.RSBSJJ2019-19);河南省科技攻关项目(No.212102310786)。

摘　　要：目的:研究重楼皂苷I(PPI)抑制食管鳞癌(ESCC)生长的分子机制。方法:MTT和平板克隆检测PPI对ESCC细胞KYSE30、KYSE450、KYSE150增殖和克隆形成能力的影响。TMT标记定量蛋白质组学分析PPI对KYSE150蛋白质组的影响。透射电镜观察PPI对KYSE150细胞形态的影响。Western Blot检测PPI对铁死亡抑制蛋白1(FSP1)和谷胱甘肽过氧化物酶4(GPX4)蛋白表达的影响。计算机建立PPI与FSP1的分子对接模型。结果:PPI抑制ESCC细胞KYSE30、KYSE450、KYSE150的增殖和克隆形成。蛋白质组学分析共鉴定到差异蛋白416个,其中上调蛋白336个,下调蛋白80个。差异蛋白富集多与细胞代谢相关,其中有7个与铁死亡相关。透射电镜观察到PPI导致KYSE150细胞线粒体体积变小,减少。PPI可与FSP1结合抑制其表达。结论:PPI可能通过抑制FSP1而非GPX4系统促进铁死亡抑制ESCC细胞生长。Objective:To investigate the molecular mechanism of polyphyllin I(PP I)inhibiting the growth of esophageal squamous cell carcinoma(ESCC).Methods:MTT and clone formation assay were used to detect the influence of PP I on the proliferation and clone formation potential of KYSE30,KYSE450 and KYSE150.TMT-labeled quantitative proteomics analysis was used to analyze the influence of PPI on the proteome of KYSE150.Transmission electron microscopy(TEM)was used to detect the effect of PP I on the morphology change of KYSE150.Western Blot was applied to measure the expression levels of ferroptosis suppressor protein 1(FSP1)and glutathione peroxidase 4(GPX4).The molecular docking model of PP I and FSP1 was established by computer.Results:PP I inhibited the proliferation and clone formation of KYSE30,KYSE450 and KYSE150.A total of 416 differential expressed proteins(DEPs)were identified by proteomic analysis,including 336 upregulated proteins and 80 down-regulated proteins.Most of the DEPs were related to cell metabolism,and 7 of which were related to ferroptosis.TEM showed that PP I caused the reduction of mitochondrial volume and mitochondrial cristae of KYSE150.PP I binding with FSP1 and inhibited its expression.Conclusion:PPI may promote ferroptosis and inhibit the growth of ESCC by inhibiting FSP1 but not GPX4 system.

关 键 词：重楼皂苷I 食管鳞癌 蛋白质组学 铁死亡 铁死亡抑制蛋白1 

分 类 号：R735.1[医药卫生—肿瘤]