Mechanism of vascular endothelial growth factor A in uterine leiomyo-ma through Cdc42/Wnt/β-catenin signaling pathway
10.3969/j.issn.1000-4718.2025.07.009
- VernacularTitle:血管内皮生长因子A通过Cdc42/Wnt/β-catenin信号通路影响子宫平滑肌瘤进展的机制研究
- Author:
Xiaoyin LI
1
;
Hui HE
;
Cuisong WU
;
Xianping WEN
Author Information
1. 池州市人民医院妇产科,安徽 池州 24700
- Publication Type:Journal Article
- Keywords:
uterine leiomyoma;
vascular endothelial growth factor A;
cell division cycle protein 42;
axitinib
- From:
Chinese Journal of Pathophysiology
2025;41(7):1325-1333
- CountryChina
- Language:Chinese
-
Abstract:
AIM:Uterine leiomyoma is the most prevalent benign tumor among women of reproductive age.This study aims to investigate the involvement of vascular endothelial growth factor A(VEGFA)in the progression of uterine leiomyoma through the cell division cycle protein 42(Cdc42)/Wnt/β-catenin signaling pathway.METHODS:Clinical data and tissue samples were collected from 36 patients who underwent either laparoscopic or open hysteromyomectomy at the Gynecology Department of Chizhou People's Hospital between January 2022 and December 2023.Immunohistochemi-cal staining was utilized to assess the expression of VEGFA and Cdc42.Cell viability was evaluated using the CCK-8 as-say,while cell proliferation was measured by EdU staining and flow cytometry.The expression levels of VEGFA,Cdc42,β-catenin,and their downstream targets,cyclin D1 and c-Myc,were analyzed via Western blot.RESULTS:Immunohis-tochemical and Western blot analyses revealed significantly higher levels of VEGFA and Cdc42 in leiomyoma tissues com-pared with normal uterine smooth muscle tissues.Further subgroup analysis via Western blot indicated that the expression levels of VEGFA and Cdc42 were elevated in intermuscular fibroids compared with submucosal and subserous fibroids.The CCK-8 assay demonstrated that VEGF receptor inhibitor axitinib effectively reduced the viability of uterine leiomyoma cells.Moreover,the proliferation capacity of uterine leiomyoma cells was significantly greater than that of normal uterine smooth muscle cells,and axitinib substantially inhibited this proliferation.Western blot results further confirmed signifi-cant increases in the expression of VEGFA,Cdc42,β-catenin,and their downstream proteins,cyclin D1 and c-Myc,in uterine leiomyoma cells.Axitinib was shown to inhibit the expression levels of Cdc42,β-catenin,and their downstream targets,cyclin D1 and c-Myc.The Cdc42 inhibitor ML141 did not affect VEGFA expression,but effectively inhibited the expression of β-catenin and its downstream target proteins,cyclin D1 and c-Myc.CONCLUSION:The VEGFA may play a significant role in the progression of uterine leiomyoma via the Cdc42/Wnt/β-catenin signaling pathway,suggesting that VEGFA could serve as a potential therapeutic target for the treatment of uterine leiomyoma.
