ArticleJournal of veterinary internal medicine2019
Effects of the potassium-sparing diuretic amiloride on chemotherapy response in canine osteosarcoma cells.
Article in Journal of veterinary internal medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Amiloride sensitizes prostate cancer cells to the reversible tyrosine kinase inhibitor lapatinib by modulating Erbb3 subcellular localization.Cellular and molecular life sciences : CMLS · 2024Article
- Repurposing Drugs in Small Animal Oncology.Animals : an open access journal from MDPI · 2022Review
- Overcoming T cell dysfunction in acidic pH to enhance adoptive T cell transfer immunotherapy.Oncoimmunology · 2022Article
- DMF ActivatesFrontiers in oncology · 2021Article
- Sodium homeostasis in the tumour microenvironment.Biochimica et biophysica acta. Reviews on cancer · 2019Review
- Effects of the potassium-sparing diuretic amiloride on chemotherapy response in canine osteosarcoma cells.Journal of veterinary internal medicine · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundOsteosarcoma (OSA) is a common bone tumor of mesenchymal origin in dogs. Chemotherapy delays metastasis, yet most dogs die of this disease within 1 year of diagnosis. The high metabolic demand of cancer cells promotes proton pump upregulation, leading to acidification of the tumor microenvironment and chemoresistance. The potassium-sparing diuretic amiloride is among a class of proton pump inhibitors prescribed for refractory heart failure treatment in dogs.
objectiveWe hypothesized that amiloride treatment improves chemotherapy response by reducing acidification in canine OSA cells. Our objective was to assess the in vitro effects of amiloride on cell viability, apoptosis, and metabolism.
methodsIn vitro study. Assessments of cell viability and apoptosis were performed after single agent or combination treatment, along with calculations of pharmacological synergism using the combination index. Protein signaling during apoptosis was evaluated by Western blotting. Metabolic profiling was performed using a Seahorse bioanalyzer.
resultsAmiloride strongly synergized with doxorubicin in combination treatment and exhibited additive or antagonistic effects with carboplatin in canine OSA cells. Combination treatment with doxorubicin significantly upregulated p53-mitochondrial signaling to activate apoptosis and downregulate Akt phosphorylation. Amiloride-treated cells further exhibited metabolic switching with reductions in glycolytic capacity and maximal respiration. CONCLUSION AND CLINICAL IMPORTANCE: Amiloride synergized with doxorubicin to potentiate apoptosis in canine OSA cells. These results justify further investigation into repurposing of amiloride as an oncology drug for the treatment of OSA in dogs.
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Registered trials
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