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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1528058
This article is part of the Research Topic Novel Therapeutics for Urological Cancers View all 4 articles
Gut Microbiota-Derived Metabolite Phenylacetylglutamine Inhibits the Progression of Prostate Cancer by Suppressing the Wnt/β-Catenin Signaling Pathway
Provisionally accepted
Jing Lv 1,2
Shengkai Jin 1,2
Yuhua Zhou 1,2 Chaowei Fu 1,2 Yang Shen 3 Bo Liu 4 Jufa Li 1 Menglu Li 2
Yuwei Zhang 2,3
Ninghan Feng 1,2*- 1 Jiangnan University, Wuxi, Jiangsu Province, China
- 2 Jiangnan University Medical Center (JUMC）, Wuxi, Liaoning Province, China
- 3 Nanjing Medical University, Nanjing, Jiangsu Province, China
- 4 School of Medicine, Nantong University, Nantong, Jiangsu Province, China
Prostate cancer is one of the most common malignant tumors among men worldwide, and current treatments still face many challenges. Therefore, researchers are continuously seeking new therapeutic methods to improve treatment efficacy and reduce side effects. Phenylacetylglutamine (PAGln), a common metabolite of the gut microbiota, has been reported to have anti-inflammatory and anti-tumor activities. This study aims to explore the impact of PAGln on prostate cancer and its potential mechanisms. We assessed cell proliferation, migration and invasion capabilities through CCK8, EdU incorporation, and colony formation assays, as well as wound healing and Transwell assays. The in vivo anti-cancer effects of PAGln were evaluated using a BALB/c nude mouse xenograft model of prostate cancer and a lung metastatic tumor model established via tail vein injection. Molecular mechanisms were investigated through qRT-PCR and Western blot analysis. PAGln inhibited the proliferation, migration and invasion of PCa cells and suppressed the growth of prostate cancer in vivo. PAGln notably increased the mRNA levels of CCNG2 in PCa cells. Importantly, the knockdown of CCNG2 weakened the effects of PAGln on PCa cells. Mechanistic studies revealed that PAGln could promote the phosphorylation of βcatenin by upregulating CCNG2, thereby inhibiting the Wnt/β-catenin signaling pathway. In summary, PAGln can effectively inhibit the proliferation, migration and invasion of PCa by upregulating CCNG2 and suppressing the Wnt/β-catenin signaling pathway.
Keywords: Phenylacetylglutamine, prostate cancer, proliferation, Migration, CCNG2, Wnt/β-catenin pathway Phenylacetylglutamine, Wnt/β-Catenin pathway
Received: 14 Nov 2024; Accepted: 13 Feb 2025.
Copyright: © 2025 Lv, Jin, Zhou, Fu, Shen, Liu, Li, Li, Zhang and Feng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ninghan Feng, Jiangnan University, Wuxi, 214122, Jiangsu Province, China
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