湖南中医药大学学报2025，Vol.45Issue(11)：2081-2089,9.DOI:10.3969/j.issn.1674-070X.2025.11.008
雷公藤红素通过miR-224-5p/EGR2通路抑制胃癌MGC803细胞生物学行为的作用机制
Mechanism of action of celastrol inhibiting biological behaviors of gastric cancer MGC803 cells via the miR-224-5p/EGR2 pathway
摘要
Abstract
Objective To investigate the effects of celastrol(CL)on the proliferation,apoptosis,and invasion of gastric cancer MGC803 cells and its underlying mechanism.Methods Human gastric cancer MGC803 cells were cultured in vitro and divided into control group,CL(0.5,1.0,2.0,4.0 μmol/L)groups,miR-224-5p inhibitor group(miR-224-5p-i group),CL combined with miR-224-5p overexpression group(CL+mimic group),CL combined with si-EGR2 group(CL+si-EGR2 group),and miR-224-5p inhibitor combined with si-EGR2 group(miR-224-5p-i+si-EGR2 group).Cell proliferation,apoptosis,migration and invasion capacities were assessed using the CCK-8 assay,flow cytometry,Transwell invasion assay,and scratch wound healing assay respectively.The expression levels of miR-224-5p,early growth response 2(EGR2),and its downstream proteins Cyclin D1,Cleaved Caspase-3,and matrix metalloproteinase-9(MMP-9)were measured by RT-qPCR and Western blot.The targeting relationship between miR-224-5p and EGR2 was verified using a dual-luciferase reporter assay.Results Compared with the control group,CL treatment resulted in reduced cell viability,number of migrating and invading cells,scratch wound healing rate,and the protein expression levels of Cyclin D1 and MMP-9 in MGC803 cells(P＜0.01),while it increased the apoptosis rate and the protein expression levels of EGR2 and Cleaved Caspase-3(P＜0.01),and decreased the expression level of miR-224-5p(P＜0.01).The dual-luciferase reporter assay confirmed that miR-224-5p specifically binds to the 3′UTR region of EGR2 to regulate its expression.Compared with the CL 2.0 μmol/L group,the CL+mimic group exhibited increased cell viability,scratch wound healing rate,and protein expression levels of Cyclin D1 and MMP-9(P＜0.05),while the apoptosis rate and protein expression levels of EGR2 and Cleaved Caspase-3 decreased(P＜0.05).Compared with the miR-224-5p-i group,the miR-224-5p-i+si-EGR2 group showed elevated cell viability,scratch wound healing rate,and expression levels of Cyclin D1 and MMP-9(P＜0.05),along with reduced apoptosis rate and expression levels of EGR2 and Cleaved Caspase-3(P＜0.05).Conclusion CL can inhibit the proliferation and invasion of MGC803 gastric cancer cells and induce apoptosis by downregulating miR-224-5p expression and relieving its inhibitory effects on EGR2.关键词
胃癌/微小RNA-224-5p/早期生长反应因子2/增殖/凋亡/侵袭Key words
gastric cancer/miRNA-224-5p/early growth response factor 2/proliferation/apoptosis/invasion分类
中医学引用本文复制引用
胡忠源,张成明,鱼涛..雷公藤红素通过miR-224-5p/EGR2通路抑制胃癌MGC803细胞生物学行为的作用机制[J].湖南中医药大学学报,2025,45(11):2081-2089,9.基金项目
陕西省重点研发计划项目(2024SF-YBXM-499). （2024SF-YBXM-499）
