恩扎鲁胺
TMPRS2型
抗雄激素
前列腺癌
抗雄激素
癌症研究
雄激素受体
前列腺
下调和上调
肺
细胞
医学
受体
生物
内科学
2019年冠状病毒病(COVID-19)
癌症
基因
遗传学
疾病
传染病(医学专业)
作者
Damien A. Leach,Andrea Mohr,Efstathios S. Giotis,Emine Cil,Ana Maria Isac,Laura L. Yates,William Barclay,Ralf M. Zwacka,Charlotte L. Bevan,Greg N. Brooke
标识
DOI:10.1038/s41467-021-24342-y
摘要
Abstract SARS-CoV-2 attacks various organs, most destructively the lung, and cellular entry requires two host cell surface proteins: ACE2 and TMPRSS2. Downregulation of one or both of these is thus a potential therapeutic approach for COVID-19. TMPRSS2 is a known target of the androgen receptor, a ligand-activated transcription factor; androgen receptor activation increases TMPRSS2 levels in various tissues, most notably prostate. We show here that treatment with the antiandrogen enzalutamide—a well-tolerated drug widely used in advanced prostate cancer—reduces TMPRSS2 levels in human lung cells and in mouse lung. Importantly, antiandrogens significantly reduced SARS-CoV-2 entry and infection in lung cells. In support of this experimental data, analysis of existing datasets shows striking co-expression of AR and TMPRSS2, including in specific lung cell types targeted by SARS-CoV-2. Together, the data presented provides strong evidence to support clinical trials to assess the efficacy of antiandrogens as a treatment option for COVID-19.
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