Repositioning of antiarrhythmics for prostate cancer treatment: a novel strategy to reprogram cancer-associated fibroblasts towards a tumor-suppressive phenotype
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View abstract on PubMed
Summary
This summary is machine-generated.Antiarrhythmic drugs can normalize cancer-associated fibroblasts (CAFs) in prostate cancer (PCa), reducing their pro-tumor effects. This suggests repositioning these drugs to create a less permissive tumor microenvironment for PCa treatment.
Area Of Science
- Oncology
- Pharmacology
- Cell Biology
Background
- Cancer-associated fibroblasts (CAFs) promote prostate cancer (PCa) progression through tumor cell interactions.
- CAFs exhibit upregulated voltage-gated cation channels compared to normal prostate fibroblasts (NPFs).
- Antiarrhythmic drugs, known cation channel inhibitors, were investigated for their effects on CAFs.
Purpose Of The Study
- To explore the impact of antiarrhythmic drugs on the activated phenotype of CAFs.
- To assess how antiarrhythmics affect CAF interactions with PCa cells.
- To investigate the potential of antiarrhythmics as a therapeutic strategy for PCa.
Main Methods
- Assessed antiarrhythmic effects on CAF morphology and activation markers.
- Evaluated CAF contractility and migration using 3D gel collagen contraction and scratch assays.
- Investigated CAF-PCa cell interplay in co-cultures, assessing tumor cell growth and EMT markers.
- Conducted in vivo studies using PCa xenografts in SCID mice.
Main Results
- Antiarrhythmics modulated CAF activation markers, reduced CAF motility, and hindered extracellular matrix remodeling (e.g., MMP-2 release).
- Antiarrhythmics partially reversed CAF-driven pro-tumor effects on PCa cell growth and plasticity.
- In vivo experiments showed reduced PCa xenograft tumor growth when treated with antiarrhythmic-conditioned medium or co-injected CAFs.
Conclusions
- Antiarrhythmic drugs can normalize the CAF phenotype, reducing their pro-tumorigenic influence.
- Repositioning antiarrhythmic drugs offers a novel therapeutic strategy for PCa.
- Targeting CAFs with antiarrhythmics may create a less permissive tumor microenvironment for prostate cancer.
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