Evidence map›Paper›PMID 39309483›Full record

ArticleActa pharmaceutica Sinica. B2024

Icaritin inhibits the progression of urothelial cancer by suppressing PADI2-mediated neutrophil infiltration and neutrophil extracellular trap formation.

Zezhong Mou, Yiling Chen, Jinzhong Hu, Yun Hu, Lujia Zou, Xinan Chen, Shenghua Liu, Qiuping Yin, Jian Gong, Shuchen Li and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta pharmaceutica Sinica. B, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed.

  1. Review
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  8. Engineered bacteria reprogram tumor microenvironmentActa pharmaceutica Sinica. B · 2026
    Article
  9. Baohuoside I CombatedAntioxidants (Basel, Switzerland) · 2026
    Article
  10. Review
  11. Article
  12. Review
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  16. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Zezhong MouDepartment of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Yiling ChenDepartment of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Jinzhong HuDepartment of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Yun HuDepartment of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Lujia ZouDepartment of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Xinan ChenDepartment of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Shenghua LiuDepartment of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Qiuping YinDepartment of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Jian GongDepartment of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Shuchen LiDepartment of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Shanhua MaoDepartment of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Chenyang XuDepartment of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Haowen JiangDepartment of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumor relapse and metastasis are the major causes of mortality associated with urothelial cancer. In the tumor microenvironment, negative regulatory molecules and various immune cell subtypes suppress antitumor immunity. The inflammatory microenvironment, associated with neutrophils and neutrophil extracellular traps (NETs), promotes tumor metastasis. However, no drugs are currently available to specifically inhibit neutrophils and NETs. In this study, we first demonstrated that icaritin (ICT), a Chinese herbal remedy that is a first-line treatment for advanced and incurable hepatocellular carcinoma, reduces NETs caused by suicidal NETosis and prevents neutrophil infiltration in the tumor microenvironment. Mechanistically, ICT binds to and inhibits the expression of PADI2 in neutrophils, thereby suppressing PADI2-mediated histone citrullination. Moreover, ICT inhibits ROS generation, suppresses the MAPK signaling pathway, and inhibits NET-induced tumor metastasis. Simultaneously, ICT inhibits tumoral PADI2-mediated histone citrullination, which consequently suppresses the transcription of neutrophil-recruiting genes such as GM-CSF and IL-6. The downregulation of IL-6 expression, in turn, forms a regulatory feedback loop through the JAK2/STAT3/IL-6 axis. Through a retrospective study of clinical samples, we found a correlation between neutrophils, NETs, UCa prognosis, and immune evasion. Combining ICT with immune checkpoint inhibitors may have synergistic effects. In summary, our study demonstrated that ICT could be a novel inhibitor of NETs and a novel UCa treatment.

Indexed as

IcaritinNeutrophilNeutrophil extracellular trapPADI2Urothelial cancer

Identifiers

PMID39309483
PMCPMC11413672

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.