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

doi:10.12259/j.issn.2095-610X.S20251107

Volume 46 Issue 11

Nov. 2025

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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, 2025, 46(11): 50-57. doi: 10.12259/j.issn.2095-610X.S20251107

Citation:

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, 2025, 46(11): 50-57. doi: 10.12259/j.issn.2095-610X.S20251107

Citation:

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, 2025, 46(11): 50-57. doi: 10.12259/j.issn.2095-610X.S20251107

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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

doi: 10.12259/j.issn.2095-610X.S20251107

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

Received Date: 2025-05-09
Available Online: 2025-11-08
Publish Date: 2025-11-25

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. 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.
- Finasteride,
- Bladder cancer,
- HIF-1α/Snail,
- Epithelial mesenchymal transition

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References(23)

References

[1]	Dobruch J, Oszczudłowski M. Bladder cancer: Current challenges and future directions[J]. Medicina (Kaunas), 2021, 57(8): 749. doi: 10.3390/medicina57080749
[2]	Lenis A T, Lec P M, Chamie K, et al. Bladder cancer[J]. Jama, 2020, 324(19): 1980-1991. doi: 10.1001/jama.2020.17598
[3]	Richters A, Aben K K H, Kiemeney L A L M. The global burden of urinary bladder cancer: An update[J]. World J Urol, 2020, 38(8): 1895-1904. doi: 10.1007/s00345-019-02984-4
[4]	陈健康, 彭道荣, 陈慧昱, 等. 尿液膀胱肿瘤抗原水平检测在膀胱癌诊断中的意义[J]. 现代检验医学杂志, 2019, 34(6): 135-137. doi: 10.3969/j.issn.1671-7414.2019.06.034
[5]	陈剑柏. 保留膀胱综合治疗对非转移性肌层浸润性膀胱癌预后影响[D]. 西安: 中国人民解放军空军军医大学, 2024.
[6]	龙恭伟, 王东文, 叶章群. 肌层浸润性膀胱癌保膀胱治疗的现状与展望[J]. 现代泌尿生殖肿瘤杂志, 2023, 15(3): 129-132. doi: 10.3870/j.issn.1674-4624.2023.03.001
[7]	Chislett B, Chen D, Perera M L, et al. 5-alpha reductase inhibitors use in prostatic disease and beyond[J]. Transl Androl Urol., 2023, 12(3): 487-496.
[8]	Crerar H, Scott Solomon E, Bodkin-Clarke C, et al. Regulation of NGF signaling by an axonal untranslated mRNA[J]. Neuron, 2019, 102(3): 553-563.e8.
[9]	Baumgartner B G, Orpinell M, Duran J , et al. Identification of a novel modulator of thyroid hormone receptor-mediated action[J]. PLoS One, 2007, 2(11): e1183.
[10]	Juri H, Narumi Y, Panebianco V, et al. Staging of bladder cancer with multiparametric MRI[J]. Br J Radiol., 2020, 93(1112): 20200116. doi: 10.1259/bjr.20200116
[11]	Rashid M, Zadeh L R, Baradaran B, et al. Up-down regulation of HIF-1α in cancer progression[J]. Gene, 2021, 798: 145796. doi: 10.1016/j.gene.2021.145796
[12]	Korbecki J, Simińska D, Gąssowska-Dobrowolska M, et al. Chronic and cycling hypoxia: Drivers of cancer chronic inflammation through HIF-1 and NF-κB activation: A review of the molecular mechanisms[J]. Int J Mol Sci, 2021, 22(19): 10701. doi: 10.3390/ijms221910701
[13]	Cowman S J, Koh M Y. Revisiting the HIF switch in the tumor and its immune microenvironment[J]. Trends Cancer, 2022, 8(1): 28-42. doi: 10.1016/j.trecan.2021.10.004
[14]	Hayes J D, Dinkova-Kostova A T, Tew K D. Oxidative stress in cancer[J]. Cancer Cell, 2020, 38(2): 167-197. doi: 10.1016/j.ccell.2020.06.001
[15]	Lee S H, Golinska M, Griffiths J R. HIF-1-independent mechanisms regulating metabolic adaptation in hypoxic cancer cells[J]. Cells, 2021, 10(9): 2371. doi: 10.3390/cells10092371
[16]	Elzakra N, Kim Y. HIF-1α metabolic pathways in human cancer[J]. Adv Exp Med Biol, 2021, 1280: 243-260.
[17]	Zhu Y, Tan J, Xie H, et al. HIF-1α regulates EMT via the Snail and β-catenin pathways in paraquat poisoning-induced early pulmonary fibrosis[J]. J Cell Mol Med, 2016, 20(4): 688-697. doi: 10.1111/jcmm.12769
[18]	De Francesco E M, Maggiolini M, Musti A M. Crosstalk between Notch, HIF-1α and GPER in breast cancer EMT[J]. Int J Mol Sci, 2018, 19(7): E2011. doi: 10.3390/ijms19072011
[19]	Li Q, Hong Y, Chen J, et al. Hypoxia-induced HIF-1α expression promotes neurogenic bladder fibrosis via EMT and pyroptosis[J]. Cells, 2022, 11(23): 3836. doi: 10.3390/cells11233836
[20]	Wieczorek E, Farooqi A A, Reszka E. Androgen receptor modulation and bladder cancer prevention - a short review[J]. Med Pr, 2022, 73(2): 151-162. doi: 10.13075/mp.5893.01229
[21]	Martínez-Rojo E, Berumen L C, García-Alcocer G, et al. The role of androgens and androgen receptor in human bladder cancer[J]. Biomolecules, 2021, 11(4): 594. doi: 10.3390/biom11040594
[22]	Tripathi A, Gupta S. Androgen receptor in bladder cancer: A promising therapeutic target[J]. Asian J Urol, 2020, 7(3): 284-290. doi: 10.1016/j.ajur.2020.05.011
[23]	La Vecchia C. Finasteride and bladder cancer[J]. Eur Urol, 2016, 69(3): 411-412. doi: 10.1016/j.eururo.2015.09.001

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