ArticleInternational journal of biological sciences2021
Discovery and Validation of Nitroxoline as a Novel STAT3 Inhibitor in Drug-resistant Urothelial Bladder Cancer.
Article in International journal of biological sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Effects of stattic and vinblastine on apoptosis and fatty acid profile in A549 lung cancer cells.Molecular biology reports · 2026Article
- ITGB4 up-regulated by STAT3 reduces the sensitivity of bladder cancer to cisplatin by suppressing p53.British journal of cancer · 2026Article
- Nitroxoline Enhances Radiosensitivity in Non-Small Cell Lung Cancer by Suppressing STAT3-AKT-MTOR Survival Signaling.International journal of molecular sciences · 2026Article
- Oleuropein regulates ubiquitination-mediated Mcl-1 turnover and exhibits antitumor activity.Cancer gene therapy · 2025Article
- Repurposing Amiodarone for Bladder Cancer Treatment.Cancer research communications · 2025Article
- Effects of Induced Pluripotent Stem Cell-Derived Astrocytes on Cisplatin Sensitivity in Pediatric Brain Cancer Cells.Cancers · 2025Article
- Article
- Mebendazole induces apoptosis and inhibits migration via the reactive oxygen species-mediated STAT3 signaling downregulation in non-small cell lung cancer.Journal of thoracic disease · 2024Article
- Application of nitroxoline in urologic oncology - a review of evidence.Contemporary oncology (Poznan, Poland) · 2024Review
- The combination treatment of RC48 and STAT3 inhibitor acts as a promising therapeutic strategy for basal bladder cancer.Frontiers in immunology · 2024Article
- Induction of Programmed Cell Death inAntioxidants (Basel, Switzerland) · 2023Article
- A sialyltransferases-related gene signature serves as a potential predictor of prognosis and therapeutic response for bladder cancer.European journal of medical research · 2023Article
- Euphorbiasteroid Induces Apoptosis as Well as Autophagy through Modulating SHP-1/STAT3 Pathway in Hepatocellular Carcinoma Cells.International journal of molecular sciences · 2023Article
- Therapeutic potential of pentamidine for glioma-initiating cells and glioma cells through multimodal antitumor effects.Cancer science · 2023Article
- Inhibitor of apoptosis proteins as therapeutic targets in bladder cancer.Frontiers in oncology · 2023Review
- Hispolon Methyl Ether, a Hispolon Analog, Suppresses the SRC/STAT3/Survivin Signaling Axis to Induce Cytotoxicity in Human Urinary Bladder Transitional Carcinoma Cell Lines.International journal of molecular sciences · 2022Article
- Nitroxoline suppresses metastasis in bladder cancer via EGR1/circNDRG1/miR-520h/smad7/EMT signaling pathway.International journal of biological sciences · 2022Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Repeated cycles of first-line chemotherapy drugs such as doxorubicin (DOX) and cisplatin (CIS) trigger frequent chemoresistance in recurrent urothelial bladder cancer (UBC). Nitroxoline (NTX), an antibiotic to treat urinary tract infections, has been recently repurposed for cancer treatment. Here we aimed to investigate whether NTX suppresses drug-resistant UBC and its molecular mechanism. The drug-resistant cell lines T24/DOX and T24/CIS were established by continual exposure of parental cell line T24 to DOX and CIS, respectively. T24/DOX and T24/CIS cells were resistant to DOX and CIS, respectively, but they were sensitive to NTX time- and dose-dependently. Overexpressions of STAT3 and P-glycoprotein (P-gp) were identified in T24/DOX and T24/CIS, which could be reversed by NTX. Western blot revealed that NTX downregulated p-STAT3, c-Myc, Cyclin D1, CDK4, CDK6, Bcl-xL, Mcl-1, and Survivin, which were further confirmed by Stattic, a selective STAT3 inhibitor. In vivo, NTX exhibited the significant anti-tumor effect in T24/DOX and T24/CIS tumor-bearing mice. These results suggested that NTX-induced P-gp reversal, G0/G1 arrest, and apoptosis in drug-resistant UBC were mediated by inhibition of STAT3 signaling. Our findings repurpose NTX as a novel STAT3 inhibitor to induce P-gp reversal, G0/G1 arrest, and apoptosis in drug-resistant UBC.
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