ArticleInternational journal of molecular sciences2019
Trifluoperazine, an Antipsychotic Drug, Effectively Reduces Drug Resistance in Cisplatin-Resistant Urothelial Carcinoma Cells via Suppressing Bcl-xL: An In Vitro and In Vivo Study.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Phenothiazine Derivatives and Their Impact on the Apoptosis Processes: A Review.Journal of applied toxicology : JAT · 2026Review
- Repurposing of nervous system drugs for cancer treatment: recent advances, challenges, and future perspectives.Discover oncology · 2025Review
- Suppression of CYLD by HER3 confers ovarian cancer platinum resistance via inhibiting apoptosis and by inducing drug efflux.Experimental hematology & oncology · 2025Article
- In silico exploration of anti-prostate cancer compounds from differential expressed genes.BMC urology · 2024Article
- Galectin-1 Promotes Gastric Carcinoma Progression and Cisplatin Resistance Through the NRP-1/c-JUN/Wee1 Pathway.Journal of gastric cancer · 2024Article
- First-Line Combination Treatment with Low-Dose Bipolar Drugs for ABCB1-Overexpressing Drug-Resistant Cancer Populations.International journal of molecular sciences · 2023Review
- TRAF4-mediated ubiquitination-dependent activation of JNK/Bcl-xL drives radioresistance.Cell death & disease · 2023Article
- The UCHL5 inhibitor b-AP15 overcomes cisplatin resistance via suppression of cancer stemness in urothelial carcinoma.Molecular therapy oncolytics · 2022Article
- Antagonizing Sec62 function in intracellular CaFrontiers in physiology · 2022Article
- The inhibitory effect and mechanism of quetiapine on tumor progression in hepatocellular carcinoma in vivo.Environmental toxicology · 2022Article
- PR-619, a General Inhibitor of Deubiquitylating Enzymes, Diminishes Cisplatin Resistance in Urothelial Carcinoma Cells through the Suppression of c-Myc: An In Vitro and In Vivo Study.International journal of molecular sciences · 2021Article
- Aberrant Bcl-x splicing in cancer: from molecular mechanism to therapeutic modulation.Journal of experimental & clinical cancer research : CR · 2021Review
- A New Platinum-Based Prodrug Candidate for Chemotherapy and Its Synergistic Effect With Hadrontherapy: Novel Strategy to Treat Glioblastoma.Frontiers in neuroscience · 2021Article
- Trifluoperazine induces cellular apoptosis by inhibiting autophagy and targeting NUPR1 in multiple myeloma.FEBS open bio · 2020Article
- Dissecting the Anticancer Mechanism of Trifluoperazine on Pancreatic Ductal Adenocarcinoma.Cancers · 2019Article
- Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Cisplatin-based chemotherapy is the primary treatment for metastatic bladder urothelial carcinoma (UC). Most patients inevitably encounter drug resistance and resultant disease relapse. Reduced apoptosis plays a critical role in chemoresistance. Trifluoperazine (TFP), an antipsychotic agent, has demonstrated antitumor effects on various cancers. This study investigated the efficacy of TFP in inhibiting cisplatin-resistant bladder UC and explored the underlying mechanism. Our results revealed that cisplatin-resistant UC cells (T24/R) upregulated the antiapoptotic factor, B-cell lymphoma-extra large (Bcl-xL). Knockdown of Bcl-xL by siRNA resensitized cisplatin-resistant cells to the cisplatin cytotoxic effect. TFP (10-45 μM) alone elicited dose-dependent cytotoxicity, apoptosis, and G0/G1 arrest on T24/R cells. Co-treatment of TFP potentiated cisplatin-induced cytotoxicity in T24/R cells. The phenomenon that TFP alleviated cisplatin resistance to T24/R was accompanied with concurrent suppression of Bcl-xL. In vivo models confirmed that TFP alone effectively suppressed the T24/R xenograft in nude mice. TFP co-treatment enhanced the antitumor effect of cisplatin on the T24/R xenograft. Our results demonstrated that TFP effectively inhibited cisplatin-resistant UCs and circumvented cisplatin resistance with concurrent Bcl-xL downregulation. These findings provide a promising insight to develop a therapeutic strategy for chemoresistant UCs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.