Effect of Tripterygium glycosides on cisplatin resistance in osteosarcoma cells via TFEB-mediated ferroptosis
GUAN Bo-ya
GE Zhen-hua
ZHANG Jin-hong
CHEN Qing
FENG Xin
Abstract：Objective To investigate the effect of Tripterygium glycosides(TG)on cisplatin resistance in osteo-sarcoma cells via regulation of transcription factor EB(TFEB)-mediated ferroptosis.Methods Osteosarcoma MG63 cells and cisplatin-resistant MG63/CDDP cells were treated with various concentrations of cisplatin(0,0.1,0.5,1.0,1.5,2.0 μmol/L)to determine IC50 values.MG63/CDDP cells treated with 2 μmol/L cisplatin were divided into:con-trol group(no additional treatment),TG groups(20,40,80,and 160 μmol/L TG),negative control(NC)group(transfected with NC siRNA),NC+TG group(transfected with NC siRNA and treated with 160 μmol/L TG),and si-TFEB+TG group(transfected with TFEB siRNA and treated with 160 μmol/L TG).Cisplatin IC50,resistance index,in-tracellular Fe2+and reactive oxygen species(ROS)levels,and protein expression of GPX4,SLC7 A1 1,and TFEB(in to-tal and nuclear protein fractions)were measured.Results The cisplatin IC50 of MG63/CDDP cells was significantly high-er than that of MG63 cells[(6.09±0.86)μmol/L vs.(1.08±0.15)μmol/L,P＜0.05].In TG-treated MG63/CD-DP cells,increasing TG concentrations were associated with decreased cisplatin IC50,resistance index,and protein levels of GPX4 and SLC7A11,while Fe2+,ROS,and nuclear TFEB expression levels increased in a dose-dependent manner.Compared with the NC+TG group,the si-TFEB+TG group showed higher cisplatin IC50,resistance index,and expres-sion of GPX4 and SLC7A11[(4.08±0.52)μmol/L,3.78±0.39,0.64±0.07,0.65±0.07 vs.(2.41±0.35)μmol/L,2.23±0.34,0.24±0.02,0.33±0.04,P＜0.05],but lower levels of Fe2+,ROS,and both total and nuclear TFEB protein[(3.51±0.47)μmol/L,(2.46±0.32)U/L,0.47±0.05,0.61±0.07 vs.(6.24±0.69)μmol/L,(4.29±0.39)U/L,1.07±0.11,1.28±0.15,P＜0.05].Conclusion TG reverses cisplatin resistance in osteosarcoma cells,potentially through activation of TFEB-mediated ferroptosis.
Keywords：osteosarcomacisplatin resistanceTripterygium glycosidestranscription factor EBferroptosis
Publication Date：2025-08-15
Online Publishing Date：2025-11-06(First online date of this platform, not the publication date of the document)
Pages：6( 1156-1161 )