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

Hongyu CHEN; Lei YANG; Xiao WANG; Ling XIE

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Hongyu CHEN, Lei YANG, Xiao WANG, Ling XIE. 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[J]. Journal of Kunming Medical University.

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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

Department of Oncology，Panzhihua Hospital of Integrated Traditional Chinese and Western Medicine，Panzhihua Sichuan 617000，China

Received Date: 2025-05-09

Abstract

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. Expression levels of HIF-1α and EMT-related proteins （E-cadherin, N-cadherin, Vimentin） were detected by Western blotting. 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 weaker tumor metastasis in mice. Conclusions Finasteride can effectively block the growth of bladder cancer and the transition of epithelial cells into mesenchymal cells by inhibiting HIF-1α/Snail expression.
- Finasteride,
- Bladder cancer,
- HIF-1α/Snail,
- Epithelial mesenchymal transition

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References(22)

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