J Cancer 2020; 11(22):6633-6641. doi:10.7150/jca.47025 This issue

Research Paper

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

Naijin Xu1,2#, Wenfeng Lin1#, Jingkai Sun1,3, Takuya Sadahira1, Abai Xu3, Masami Watanabe1,4, Kai Guo3, Motoo Araki1, Gonghui Li2, Chunxiao Liu3, Yasutomo Nasu1,4, Peng Huang1,3,5✉

1. Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
2. Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
3. Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
4. Center for Innovative Clinical Medicine, Okayama University Hospital
5. Okayama Medical Innovation Center, Okayama University, Okayama, Japan
# These authors contributed to the work equally and should be regarded as co-first authors.

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Citation:
Xu N, Lin W, Sun J, Sadahira T, Xu A, Watanabe M, Guo K, Araki M, Li G, Liu C, Nasu Y, Huang P. Nitroxoline inhibits bladder cancer progression by reversing EMT process and enhancing anti-tumor immunity. J Cancer 2020; 11(22):6633-6641. doi:10.7150/jca.47025. Available from https://www.jcancer.org/v11p6633.htm

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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. In vitro 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.

Keywords: Nitroxoline, Bladder cancer, EMT, immunotherapy preclinical model