5α-还原酶的基因组改变及其抑制剂非那雄胺在膀胱癌中的作用
The Genomic Alterations of 5α-Reductases and Their Inhibitor Finasteride's Effect in Bladder Cancer.
作者信息
Chen Chi-Cheng, Huang Chi-Ping, Tsai Yi-Tung, Hseih Teng-Fu, Shyr Chih-Rong
机构信息
Sex Hormone Research Center, Departments of Medical Laboratory Science and Biotechnology and Urology, Graduate Institute of Clinical Medical Science, China Medical University and Hospital, Taichung, Taiwan, R.O.C.
Department of Urology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan, R.O.C.
出版信息
Anticancer Res. 2017 Dec;37(12):6893-6898. doi: 10.21873/anticanres.12152.
BACKGROUND/AIM: Since androgens affect urothelial bladder cancer (UBC), we examined whether 5α-reductases (5-AR) have genomic alterations in UBC and whether 5α-reductase inhibitors (5-ARI) affect UBC.
MATERIALS AND METHODS
The cBioPortal was used to analyze genomic alternations of 5-ARs in UBC cancer genomic datasets. Next, we used the Taiwan National Health Insurance Research database to conduct a population-based case-control study to investigate the effect of a 5-ARI, finasteride on UBC incidence. We also performed an XTT assay to examine the direct effect of finasteride on UBC cells.
RESULTS
We found that 5-AR genomic alternations were observed in 29% of UBC patients and patients with alternations had shorter disease-free survival. Also, the use of finasteride with >180 cDDDs reduced the risk of UBC. Finasteride could directly inhibit UBC cell growth.
CONCLUSION
Based on our findings, we concluded that 5-AR could be explored as a therapeutic target for UBC with 5-ARIs.
背景/目的：由于雄激素会影响膀胱尿路上皮癌（UBC），我们研究了5α-还原酶（5-AR）在UBC中是否存在基因组改变以及5α-还原酶抑制剂（5-ARI）是否会影响UBC。
材料与方法
利用cBioPortal分析UBC癌症基因组数据集中5-AR的基因组改变。接下来，我们使用台湾国民健康保险研究数据库进行一项基于人群的病例对照研究，以调查5-ARI非那雄胺对UBC发病率的影响。我们还进行了XTT试验，以研究非那雄胺对UBC细胞的直接作用。
结果
我们发现29%的UBC患者存在5-AR基因组改变，且有改变的患者无病生存期较短。此外，使用非那雄胺累积限定日剂量（cDDD）>180可降低UBC风险。非那雄胺可直接抑制UBC细胞生长。
结论
基于我们的研究结果，我们得出结论，5-AR可作为使用5-ARI治疗UBC的一个治疗靶点进行探索。
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