山西医科大学学报2025，Vol.56Issue(7)：736-744,9.DOI:10.13753/j.issn.1007-6611.2025.07.002
瑞马唑仑联合七氟醚对胃癌细胞转移的抑制作用及机制
Inhibitory effect and mechanism of remimazolam combined with sevoflurane on metastasis of gastric cancer cells
摘要
Abstract
Objective To explore the regulatory effect and mechanism of polarization of tumor-associated macrophages(TAM)induced by Remimazolam(Rem)combined with Sevoflurane(Sev)on the metastasis of gastric cancer cells.Methods THP-1 cells were treated with phorbol 12-myristate 13-acetate(PMA)at a final concentration of 320 ng/mL for 12 h to induce M0-type TAMs(M0-TAMs).Subsequently,cells were stimulated with PMA(100 ng/mL),interleukin-4(IL-4,20 ng/mL),and interleukin-13(IL-13,20 ng/mL)for 48 h to induce M2-type TAMs(M2-TAMs).Human gastric cancer HGC-27 cells were randomly assigned to control group,Rem group,Sev group,and Rem+Sev group.Cells from each group were collected and co-cultured with either M0-TAMs or M2-TAMs using a Transwell co-culture system.Cell proliferation was assessed by colony formation assay,and cell migration and invasion were evalu-ated using Transwell assays.Macrophage polarization was analyzed by flow cytometry.Levels of transforming growth factor-β(TGF-β),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-1β in the co-culture supernatant were quantified by enzyme-linked im-munosorbent assay(ELISA).Western blotting was employed to detect the expressions of macrophage polarization markers arginase-1(Arg-1)and inducible nitric oxide synthase(iNOS),epithelial-mesenchymal transition(EMT)-related proteins,including E-cad-herin,Vimentin,zinc finger E-box-binding homeobox 1(ZEB1),Twist,and smad pathway-related proteins phosphorylated smad2(p-smad2),phosphorylated smad3(p-smad3),and total smad2/3.Results Compared with Sev group,colony formation,migration,and invasion of gastric cancer cells significantly reduced in Rem+Sev group(P＜0.05).In the M0-TAM and HGC-27 co-culture system,compared with Sev group,Arg-1 expression in macrophages and IL-10 levels in the supernatant were decreased in Rem+Sev group(P＜0.05),while iNOS expression and TNF-α and IL-1β levels were increased(P＜0.05).In the M2-TAM and HGC-27 co-culture system,compared with Sev group,the number of colony formation and the migration and invasion of HGC-27 cells were decreased in Rem+Sev group(P＜0.05),the expression of E-cadherin was elevated(P＜0.05),and the expressions of Vimentin,ZEB1 and Twist were reduced(P＜0.05),and TGF-β content and p-smad2 and p-smad3 expressions were elevated(P＜0.05).Conclusion Rem combined with Sev may inhibit TGF-β/smad pathway-mediated EMT in gastric cancer cells by modulating TAM polarization,thereby suppressing the pro-liferation,invasion,and metastasis of gastric cancer cells.关键词
瑞马唑仑/七氟醚/肿瘤相关巨噬细胞/胃癌/上皮-间充质转化/TGF-β/smad信号通路Key words
Remimazolam/Sevoflurane/tumor-associated macrophages/gastric cancer/epithelial-mesenchymal transition/TGF-β/smad signaling pathway分类
医药卫生引用本文复制引用
赵昆,马宾,谢金兰..瑞马唑仑联合七氟醚对胃癌细胞转移的抑制作用及机制[J].山西医科大学学报,2025,56(7):736-744,9.基金项目
山东省医药科技项目(202205031071) （202205031071）
