中国医院用药评价与分析2025，Vol.25Issue(8)：918-923,927,7.DOI:10.14009/j.issn.1672-2124.2025.08.004
瑞马唑仑通过调控HMGB1/TLR4/NF-κB通路促进卵巢癌细胞焦亡的作用机制研究
Mechanism of Remazolam in Promoting Pyroptosis of Ovarian Cancer Cells by Regulating HMGB1/TLR4/NF-κB Pathway
摘要
Abstract
OBJECTIVE:To probe into the effect of remimazolam(Rem)in regulating pyroptosis on malignant biological behavior of ovarian cancer(OC)cells,and explore the possible mechanism of high mobility group protein B1(HMGB1)/Toll-like receptor(TLR)4/nuclear factor κB(NF-κB)pathway.METHODS:Human OC cell SKOV3 was used as the research object,and the effective intervention concentration of Rem screened by Methylthiazolyldiphenyl-tetrazolium bromide method was divided into the control group,Rem low-dose(2.5 μmol/L)group,Rem medium-dose(5 μmol/L)group,Rem high-dose(10 μmol/L)group,Rem+si-NC group and Rem+si-HMGB1 group.Colony formation assay,Transwell assay and flow cytometry were used to detect cell proliferation,migration,invasion and apoptosis.Inverted microscope was used to observe the morphologic changes of the cells in each group.Dihydroethidium(DHE)staining was used to assess the production of reactive oxygen species(ROS).The corresponding kit was used to detect the rate of lactate dehydrogenase(LDH)leakage and the content of interleukin(IL)-1β and IL-18 in the supernatant of the culture medium.Western blot was used to detect the pyroptosis and HMGB1/TLR4/NF-κB pathway-related protein expression.RESULTS:Compared with 0 μmol/L Rem-treated SKOV3 cells,the cell survival rate decreased after 1.25 to 20 μmol/L Rem treatment for 48 h,with statistically significant differences(P<0.05).Compared with control group,SKOV3 cells in the Rem low-,medium-and high-dose groups showed a decrease in the number of colony forming,migrating and invading cells,a increase in the apoptosis rate,a decrease in the number of cells,obvious cytoplasmic swelling and membrane rupture accompanied by the phenomenon of bubbly protruding material emerging,and a increase in the levels of ROS,rate of LDH leakage,contents of IL-1β and IL-18,expression of nucleotide-binding domain leucine-rich repeat-containing receptor 3(NLRP3),apoptosis-associated speck-like protein(ASC),cleaved-caspase-1,N-terminal fragment of dermatan D(GSDMD-N),HMGB1,TLR4 and NF-κB proteins,with statistically significant differences(P<0.05).Compared with the Rem+si-NC group,SKOV3 cells in the Rem+si-HMGB1 group showed decreased expression of NLRP3,ASC,cleaved-caspase-1,GSDMD-N,HMGB1,TLR4 and NF-κB proteins,increased cell survival rate,and decreased apoptosis rate,LDH leakage,content of IL-1β and IL-18,the difference was statistically significant(P<0.05).CONCLUSIONS:Rem could inhibit OC cell proliferation,migration and invasion and promote apoptosis and cell injury,and the mechanism may be related to the activation of HMGB1/TLR4/NF-κB pathway to induce OC cell pyroptosis.关键词
瑞马唑仑/卵巢癌/焦亡/高迁移率族蛋白B1/Toll样受体4/核因子κB通路Key words
Remimazolam/Ovarian cancer/Pyroptosis/HMGB1/TLR4/NF-κB pathway分类
医药卫生引用本文复制引用
杨小会,韩毅,吴立丽..瑞马唑仑通过调控HMGB1/TLR4/NF-κB通路促进卵巢癌细胞焦亡的作用机制研究[J].中国医院用药评价与分析,2025,25(8):918-923,927,7.基金项目
山西省基础研究计划(No.20210302123266) （No.20210302123266）
