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基于蛋白组学研究醋酸棉酚治疗子宫肌瘤的作用机制
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| 篇名： | 基于蛋白组学研究醋酸棉酚治疗子宫肌瘤的作用机制 |
| TITLE： | Study on the mechanism of gossypol acetic acid in the treatment of uterine fibroids based on proteomics |
| 摘要： | 目的 研究醋酸棉酚（GAA）治疗子宫肌瘤的作用机制。方法以人子宫肌瘤细胞SK-UT-1为研究对象，考察不同质量浓度（5、10、20、40、80、160μmol/L）GAA对细胞增殖活性的影响；结合四维数据非依赖型采集（4D-DIA）蛋白组学技术和生物信息学分析筛选差异蛋白，并进行基因本体（GO）分析和京都基因与基因组百科全书（KEGG）信号通路分析；检测SK-UT-1细胞中差异倍数排前3名的蛋白[N-myc下游调节基因1（NDRG1）、表皮生长因子受体反馈抑制剂1（ERRFI1）、CXC趋化因子配体3（CXCL3）]的表达水平。结果10～160μmol/L的GAA可显著降低细胞存活率（P＜0.05）。蛋白组学结果显示，共获取了921个差异蛋白，其中上调蛋白254个、下调蛋白667个，差异蛋白主要分布在线粒体、细胞核、细胞外基质等。生物信息学结果显示，差异蛋白涉及的信号通路主要有PI3K/AKT（磷脂酰肌醇3激酶/蛋白激酶B）、MAPK（促分裂原活化的蛋白质激酶）、TNF（肿瘤坏死因子）等，主要涉及细胞凋亡、衰老、运动。GAA可显著下调细胞中NDRG1、CXCL3蛋白表达水平（P＜0.05），显著上调ERRFI1蛋白表达水平（P＜0.05）。结论GAA对子宫肌瘤的改善作用可能涉及PI3K/AKT、MAPK、TNF等信号通路；其可通过下调NDRG1、CXCL3蛋白的表达，上调ERRFI1蛋白的表达，影响子宫肌瘤细胞的增殖和凋亡，从而改善子宫肌瘤的发生发展。 |
| ABSTRACT： | OBJECTIVE To investigate the mechanism of gossypol acetic acid （GAA） in the treatment of uterine fibroids. METHODS Human leiomyoma cells SK-UT-1 were selected as objects to investigate the effects of different concentrations （5， 10， 20， 40， 80， 160 μmol/L） of GAA on the activities of cell proliferation. 4D-DIA proteomic detection and bioinformatics analysis were carried out to screen differential proteins. Gene ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway analysis were performed. The expressions of top 3 proteins [N-myc downstream regulated gene 1 （NDRG1）， epidermal growth factor receptor feedback inhibitor 1 （ERRFI1）， CXC chemokine ligand 3 （CXCL3）] with differential fold changes in SK-UT-1 cells were determined. RESULTS 10-160 μmol/L GAA could significantly reduce the survival rate of SK- UT-1 cells （P＜0.05）. Proteomics results showed that a total of 921 differentially expressed proteins were obtained， including 254 up-regulated proteins and 667 down-regulated proteins. The differentially expressed proteins were mainly distributed in mitochondria， nucleus， extracellular matrix， etc. Bioinformatics results showed that differentially expressed proteins were mainly involved in signaling pathways such as PI3K/AKT （phosphoinositide 3-kinase/protein kinase B）， MAPK （mitogen-activated protein kinase）， TNF （tumor necrosis factor）， etc.， which mainly involved cell apoptosis， aging， and movement. GAA significantly decreased protein expressions of NDRG1 and CXCL3 （P＜0.05）， but increased protein expression of ERRFI1 （P＜0.05）. CONCLUSIONS The improvement effect of GAA on uterine fibroids may involve signaling pathways such as PI3K/AKT， MAPK， TNF， etc. It can improve the occurrence and development of uterine fibroids by downregulating the expressions of NDRG1 and CXCL3 proteins， upregulating the expression of ERRFI1 protein， and affecting the proliferation and apoptosis of uterine fibroid cells. |
| 期刊： | 2025年第36卷第03期 |
| 作者： | 张歆；古丽斯坦·阿不来提；沈静；张裴；马祖文；姚军 |
| AUTHORS： | ZHANG Xin，Gulisitan·Abulaiti ，SHEN Jing，ZHANG Pei，MA Zuwen，YAO Jun |
| 关键字： | 醋酸棉酚；子宫肌瘤；蛋白组学；生物信息学；作用机制 |
| KEYWORDS： | gossypol acetic acid； uterine fibroids； proteomics； bioinformatics； mechanism |
| 阅读数： | 5 次 |
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