Molecular Mechanism of Finasteride Inhibition of Epithelial-to-Mesenchymal Transition in Bladder Cancer Cells under Hypoxia-Inducible Factor 1-alpha/Snail Family Transcriptional Repressor 1 Pathway
10.12259/j.issn.2095-610X.S20251107
- VernacularTitle:HIF-1α/Snail通路影响非那雄胺抑制膀胱癌细胞上皮间充质转化的分子机制研究
- Author:
Hongyu CHEN
1
;
Lei YANG
;
Xiao WANG
;
Ling XIE
Author Information
1. 攀枝花市中西医结合医院肿瘤科,四川 攀枝花 617000
- Keywords:
Finasteride;
Bladder cancer;
HIF-1α/Snail;
Epithelial mesenchymal transition
- From:
Journal of Kunming Medical University
2025;46(11):50-57
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects and mechanism of finasteride on epithelial mesenchymal transition in bladder urothelial carcinoma.Methods T24 human bladder cancer cells were treated with different concentrations of finasteride(0.1%,0.5%,and 1%)for 24 hours,with untreated T24 cells as the control group.Some cells were subjected to hypoxic conditions(1%O2)to mimic a low-oxygen microenvironment.Cell proliferation was assessed by immunofluorescence staining for Ki-67.Apoptosis rates were evaluated using Annexin V-FITC/PI double staining followed by flow cytometry,and cell migration was analyzed via scratch wound assays.Western blot was used to detect the expression of EMT-related proteins such as HIF-1α,E-cadherin,N-cadherin,and Vimentin.To further validate the role of the HIF-1α pathway in finasteride's anti-tumor effects,a HIF-1α overexpression lentiviral vector(MOP-1)was constructed and transfected into T24 cells.For animal experiment,T24 tumor-bearing nude mice were randomly divided into four groups:control,MOP-1,1%finasteride,and 1%finasteride+MOP-1(n=4 per group).After 4 weeks of continuous oral administration,tumor growth,metastasis,and perihepatic lymph node changes were recorded,and histological analysis was performed using H&E staining.Results Finasteride affects the proliferation,apoptosis,and epithelial-to-mesenchymal transition of T24 cells in a concentration-dependent manner.Compared to the control group,finasteride-treated T24 cells showed a reduced number of cells in the growth phase,decreased migration,increased expression of epithelial markers,and decreased expression of mesenchymal markers(P<0.05).In T24 cells exposed to hypoxic conditions,the expression of HIF-1α pathway markers was significantly increased(P<0.05),while 1%finasteride treatment inhibited the HIF-1α pathway(P<0.05).The HIF-1α pathway expression level in the 1%finasteride and HIF-1α overexpression plasmid group was lower than that in the control group(P<0.05).Additionally,the tumor mass-to-body weight ratios were lower,with the number of bladder cancer metastases to the liver decreased(P<0.05).Conclusion Finasteride can effectively block the growth of bladder cancer and the transition of epithelial cells into mesenchymal cells by inhibiting HIF-1α/Snail expression.
