Nitroxoline inhibits bladder cancer progression by reversing EMT process and enhancing anti-tumor immunity
Naijin Xu1,2, Wenfeng Lin1, Jingkai Sun1,3
1Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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.
Insights
Nitroxoline effectively inhibits bladder cancer cell growth and migration. This study reveals nitroxoline
Area of Science:
- Oncology
- Pharmacology
Background:
- Nitroxoline is an established urinary tract infection treatment.
- Emerging research indicates nitroxoline possesses anti-cancer properties.
- Its role in bladder cancer therapy remains underexplored.
Purpose of the Study:
- To investigate the anti-tumor mechanisms of nitroxoline in bladder cancer.
- To evaluate nitroxoline's efficacy in preclinical bladder cancer models.
Main Methods:
- In vitro assays assessed bladder cancer cell growth and migration.
- Western blot analysis examined epithelial-mesenchymal transition (EMT) markers.
- In vivo studies utilized a C3H/He mice bladder cancer model.
- Flow cytometry quantified myeloid-derived suppressor cells (MDSC).
Main Results:
- Nitroxoline inhibited bladder cancer cell proliferation and migration in a dose-dependent manner.
- Nitroxoline downregulated key proteins associated with EMT.
- Tumor growth was significantly suppressed in the in vivo model.
- Nitroxoline treatment led to a notable reduction in MDSC percentages.
Conclusions:
- Nitroxoline demonstrates significant anti-bladder cancer activity.
- Nitroxoline's mechanisms involve inhibiting EMT and reducing MDSCs.
- Nitroxoline shows promise as a potential therapeutic agent for bladder cancer.
