Phillyrin inhibits the proliferation,invasion,and epithelial-mesenchymal transition of glioma U251 cells via the HMGB1/RAGE signaling pathway
10.3872/j.issn.1007-385x.2025.10.007
- VernacularTitle:连翘苷经HMGB1/RAGE通路抑制胶质瘤U251细胞的增殖、侵袭及上皮间质转化
- Author:
Ming LIU
1
;
Xiaosong FENG
1
;
Yin ZHANG
1
;
Xipeng LIU
1
;
Yongda LIU
1
;
Xiufeng ZHANG
1
;
Jianxin QIAO
1
Author Information
1. 河北北方学院附属第一医院 神经外科,河北 张家口 075000
- Publication Type:Journal Article
- Keywords:
phillyrin(PHN);
high mobility group protein B1(HMGB1);
receptor of advanced glycation endproduct(RAGE);
glioma;
U251 cell;
proliferation;
invasion;
epithelial-mesenchymal transition(EMT)
- From:
Chinese Journal of Cancer Biotherapy
2025;32(10):1053-1059
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of phillyrin(PHN)on the proliferation,invasion,and epithelial-mesenchymal transition(EMT)of glioma U251 cells by adjusting the high mobility group protein B1(HMGB1)/receptor of advanced glycation endproduct(RAGE)signaling pathway.Methods:Human glioma U251cells were assigned into the PHN-0 group(treated with 0 μmol/L PHN),the low,medium,and high-dose PHN groups(PHN-50、PHN-100、PHN-200 groups,treated with 50,100,and 200 μmol/L PHN respectively),the PHN+pcDNA-NC group(treated with 200 μmol/L PHN after transfection of pcDNA-NC plasmid),and the PHN+HMGB1 group(treated with 200 μmol/L PHN after transfection of overexpressed HMGB1 plasmid).The proliferation ability of cells in each group was detected by the CCK-8 method and the clone formation assay.The apoptosis level of cells in each group was detected by flow cytometry.The migration and invasion abilities of cells in each group were detected by the Transwell assay.ELISA was used to detect the IL-8 secretion level of cells in each group.Immunofluorescence was used to detect the positive rates of N-cadherin and E-cadherin in cells of each group.WB assay was performed to detect the expression levels of Toll like receptor 4(TLR4),nuclear factor-kappa B(NF-κ B),HMGB1,RAGE,N-cadherin,E-cadherin,cell cycle protein D1(cyclin D1),cyclin dependent kinase 2(CDK2),B-lymphoblastoma-2(Bcl-2),Bcl-2 associated X protein(BAX)proteins in cells of each group.Results:Compared with those in the PHN-0 group,the proliferation activity,the number of clone formation,the numbers of invasion and migration,IL-8 secretion levels,the positive rate and protein expression of N-cadherin,and the expressions of TLR4,NF-κB,HMGB1,RAGE,cyclin D1 and CDK2 protein in the PHN-50,PHN-100,and PHN-200 groups decreased significantly(all P<0.05);and the apoptosis rate,the positivity rate and protein expression of E-cadherin,and the BAX/Bcl-2 ratio increased significantly(all P<0.05).At the same time,overexpression of HMGB1 could reverse the inhibitory effects of PHN on the proliferation,migration,invasion and EMT of U251 cells,as well as its promoting effect on the apoptosis(all P<0.05).Conclusion:PHN inhibits the proliferation,invasion and EMT progression of glioma U251 cells through the HMGB1/RAGE signaling pathway.