Knockdown of IGFBP7 promotes temozolomide sensitivity in glioma cells by inducing DNA damage and cellular senescence
10.7644/j.issn.1674-9960.2025.10.002
- VernacularTitle:敲低胰岛素样生长因子结合蛋白7通过诱导DNA损伤和细胞衰老促进胶质瘤细胞替莫唑胺敏感性
- Author:
Xiaoen GENG
1
;
Zhijia SUN
;
Jiangbo LI
;
Zhe ZHOU
Author Information
1. 军事科学院军事医学研究院,北京 100850
- Keywords:
insulin-like growth factor binding protein 7;
glioma;
temozolomide;
DNA damage;
senescence
- From:
Military Medical Sciences
2025;49(10):728-737
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of insulin-like growth factor binding protein 7(IGFBP7)on the sensitivity of glioma cells to temozolomide(TMZ)and the related mechanism.Methods IGFBP7 mRNA expression levels in TMZ-sensitive(U87 TMZ-S,U251 TMZ-S)and TMZ-resistant(U87 TMZ-R,U251 TMZ-R)glioma cells were analyzed using RNA sequencing data from the gene expression omnibus(GEO)dataset GSE151680.TMZ-resistant U87 and U251 cell lines were established via stepwise dose escalation.IGFBP7 expressions in TMZ-R cells were detected by quantitative real-time PCR(qPCR)and Western blotting.IGFBP7 was stably knock-downed in TMZ-R cells while IGFBP7 was stably overexpressed in TMZ-S cells using lentiviral infection.Cell viability,migration,invasion and TMZ sensitivity were assessed using CCK-8 assay,apoptosis assay,wound healing assay,Transwell invasion assay and colony formation assay respectively.Cellular senescence was detected by β-galactosidase(SA-β-Gal)staining.The expression levels of senescence molecular markers cyclin-dependent kinase inhibitor 1(p21)and tumor protein p53(p53),as well as DNA damage marker γ-H2A histone family member X(γ-H2AX)were determined by Western blotting.The differences in mRNA expressions of IGFBP7 between glioma tissues and normal tissues as well as the correlations with the overall survival of glioma patients were analyzed using the cancer genome atlas(TCGA),Chinese Glioma Genome Atlas(CGGA),genotype-tissue expression(GTEx)database.Results Compared to normal glioma cells,IGFBP7 expressions were significantly elevated in TMZ-R glioma cells.Overexpression of IGFBP7 in TMZ-S glioma cells enhanced cell viability but suppressed apoptosis following TMZ treatment.The expressions of senescence-associated marker(p21,p53)and DNA damage marker(γ-H2AX)were upregulated in these cells.Notably,IGFBP7 expressions were significantly higher in glioma tissues than in normal tissues,and high IGFBP7 expressions were associated with poor prognosis in glioma patients.Conclusion Knockdown of IGFBP7 promotes TMZ-induced cell senescence and DNA damage,thereby enhancing the sensitivity of gliomas cells to TMZ.
