昆明医科大学学报2025，Vol.46Issue(11)：50-57,8.DOI:10.12259/j.issn.2095-610X.S20251107
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
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
摘要
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.关键词
非那雄胺/膀胱癌/HIF-1α/Snail/上皮-间质转化Key words
Finasteride/Bladder cancer/HIF-1α/Snail/Epithelial mesenchymal transition分类
医药卫生引用本文复制引用
陈泓羽,杨蕾,王潇,谢玲..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[J].昆明医科大学学报,2025,46(11):50-57,8.基金项目
四川省卫生健康委员会科研基金(20211902) （20211902）
