Protective effect and mechanism of genistein on etoposide-induced chondrocyte senescence
10.19405/j.cnki.issn1000–1492.2026.04.007
- VernacularTitle:金雀异黄酮对依托泊苷诱导软骨细胞衰老的保护作用及其机制
- Author:
Jinhong WANG
1
;
Tianyu CHEN
1
;
Lifang MAO
1
;
Yingjie ZHAO
1
;
Renpeng ZHOU
1
;
Wei HU
1
;
Chao LU
1
Author Information
1. School of Pharmacy， Anhui Medical University， Hefei 230032
- Publication Type:Journal Article
- Keywords:
genistein;
Prdx6;
chondrocytes;
senescence;
molecular docking;
etoposide
- From:
Acta Universitatis Medicinalis Anhui
2026;61(4):636-643
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the protective effect of genistein （Gen） on etoposide-induced chondrocyte senescence and its underlying mechanism. MethodsThe C28/I2 cell line was treated with different concentrations of Gen and etoposide， and the cell viability was detected by the CCK-8 assay. The senescence model of C28/I2 chondrocytes was induced by etoposide， with Gen intervention. Senescence-associated β-galactosidase （SA-β-gal） staining was performed to detect the senescence-positive rate and staining characteristics of chondrocytes. The expressions of peroxiredoxin 6 （Prdx6）， cyclin-dependent kinaseto clarify the functional necessity of Prdx6. ResultsCompared with the etoposide group， the C28/I2 chondrocyte viability significantly increased （P<0.01）， the expression ofsenescence-associated proteins p21 and p16 decreased （P<0.01， P<0.05）， the expression of senescence-associated genes p21 and p16 reduced （both P<0.01）， the fluorescence intensity of senescence-associated proteins p21 and p16 was diminished （P<0.05， P<0.01）， and the proportion of SA-β-gal-positive cells decreased （P<0.01） in the Gen+etoposide group. Compared with the Control group， the expression of Prdx6 was downregulated in the etoposide group （P<0.05）. Compared with the etoposide group， the expression of Prdx6 was upregulated in the Gen+etoposide group （P<0.01）. Compared with the Control group， the GPx activity significantly decreased in the si-Prdx6 group （P<0.01）. Furthermore， compared with the si-Prdx6 group， the GPx activity increased in the si-Prdx6+Gen group （P<0.05）. Molecular docking results revealed that Gen formed hydrogen bond interactions with the active site of Prdx6. After Prdx6 knockdown， the expression of senescence-associated genes p21 and p16 and the fluorescence intensity of senescence-associated proteins p21 and p16 both increased in the Gen+etoposide+si-Prdx6 group （both P<0.01）. ConclusionGen can inhibit etoposide-induced senescence of C28/I2 chondrocytes by upregulating the expression of Prdx6. This study provides potential drug targets and experimental basis for the prevention and treatment of chondrocyte senescence-related diseases.
