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硝氧喹啉通过逆转上皮-间质转化过程和增强抗肿瘤免疫力来抑制膀胱癌进展。

Nitroxoline inhibits bladder cancer progression by reversing EMT process and enhancing anti-tumor immunity.

作者信息

Xu Naijin, Lin Wenfeng, Sun Jingkai, Sadahira Takuya, Xu Abai, Watanabe Masami, Guo Kai, Araki Motoo, Li Gonghui, Liu Chunxiao, Nasu Yasutomo, Huang Peng

机构信息

Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

J Cancer. 2020 Sep 23;11(22):6633-6641. doi: 10.7150/jca.47025. eCollection 2020.

DOI:10.7150/jca.47025
PMID:33046984
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7545671/
Abstract

Nitroxoline is considered to be an effective treatment for the urinary tract infections. Recently, it has been found to be effective against several cancers. However, few studies have examined the anti-tumor activity of nitroxoline in bladder cancer. The purpose of the study was to reveal the possible mechanisms how nitroxoline inhibited bladder cancer progression. assay, we demonstrated that nitroxoline inhibited bladder cancer cell growth and migration in a concentration-related manner. Western blot analysis demonstrated that nitroxoline downregulated the expressions of epithelial mesenchymal transition (EMT)-related proteins. Furthermore, treatment with nitroxoline in the C3H/He mice bladder cancer subcutaneous model resulted in significant inhibition of tumor growth. Moreover, the percentage of myeloid-derived suppressor cells (MDSC) in peripheral blood cells significantly decreased after treatment of nitroxoline. Taken together, our results suggested that nitroxoline may be used as a potential drug for bladder cancer.

摘要

硝氧喹啉被认为是治疗尿路感染的有效药物。最近，人们发现它对几种癌症也有疗效。然而，很少有研究探讨硝氧喹啉在膀胱癌中的抗肿瘤活性。本研究的目的是揭示硝氧喹啉抑制膀胱癌进展的可能机制。实验表明，硝氧喹啉以浓度相关的方式抑制膀胱癌细胞的生长和迁移。蛋白质印迹分析表明，硝氧喹啉下调上皮-间质转化（EMT）相关蛋白的表达。此外，在C3H/He小鼠膀胱癌皮下模型中用硝氧喹啉治疗可显著抑制肿瘤生长。而且，硝氧喹啉治疗后外周血细胞中髓源性抑制细胞（MDSC）的百分比显著降低。综上所述，我们的结果表明硝氧喹啉可能作为一种潜在的膀胱癌治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03db/7545671/84414539e587/jcav11p6633g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03db/7545671/6893e4894153/jcav11p6633g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03db/7545671/1704cd7b3c4b/jcav11p6633g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03db/7545671/2a2528bcb713/jcav11p6633g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03db/7545671/8f462fc9fe52/jcav11p6633g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03db/7545671/84414539e587/jcav11p6633g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03db/7545671/6893e4894153/jcav11p6633g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03db/7545671/1704cd7b3c4b/jcav11p6633g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03db/7545671/2a2528bcb713/jcav11p6633g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03db/7545671/8f462fc9fe52/jcav11p6633g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03db/7545671/84414539e587/jcav11p6633g006.jpg

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本文引用的文献

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Integrative proteomic and functional analyses provide novel insights into the action of the repurposed drug candidate nitroxoline in AsPC-1 cells.综合蛋白质组学和功能分析为重新定位药物候选物硝呋太尔在 AsPC-1 细胞中的作用提供了新的见解。
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Organoruthenated Nitroxoline Derivatives Impair Tumor Cell Invasion through Inhibition of Cathepsin B Activity.
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Nitroxoline suppresses metastasis in bladder cancer via EGR1/circNDRG1/miR-520h/smad7/EMT signaling pathway.硝呋太尔通过 EGR1/circNDRG1/miR-520h/smad7/EMT 信号通路抑制膀胱癌转移。
Int J Biol Sci. 2022 Aug 8;18(13):5207-5220. doi: 10.7150/ijbs.69373. eCollection 2022.
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Discovery and Validation of Nitroxoline as a Novel STAT3 Inhibitor in Drug-resistant Urothelial Bladder Cancer.发现硝呋太尔是一种新型 STAT3 抑制剂，可用于治疗耐药性膀胱癌。
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