Assessing the Therapeutic Efficacy of Proton Transport Inhibitors in a Triple-Negative Breast Cancer Murine Model with Magnetic Resonance Imaging-Chemical Exchange Saturation Transfer Tumor pH Imaging.

Autor:	Dhakan C; Institute of Biostructures and Bioimaging (IBB), National Research Council of Italy (CNR), Via Nizza 52, 10126 Turin, Italy., Anemone A; Department of Molecular Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126 Turin, Italy., Ventura V; Department of Molecular Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126 Turin, Italy., Carella A; Institute of Biostructures and Bioimaging (IBB), National Research Council of Italy (CNR), Via Nizza 52, 10126 Turin, Italy., Corrado A; Institute of Biostructures and Bioimaging (IBB), National Research Council of Italy (CNR), Via Nizza 52, 10126 Turin, Italy., Pirotta E; Institute of Biostructures and Bioimaging (IBB), National Research Council of Italy (CNR), Via Nizza 52, 10126 Turin, Italy., Villano D; Department of Molecular Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126 Turin, Italy., Romdhane F; Institute of Biostructures and Bioimaging (IBB), National Research Council of Italy (CNR), Via Nizza 52, 10126 Turin, Italy., Gammaraccio F; Department of Molecular Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126 Turin, Italy., Aime S; IRCCS SynLAB SDN, Via Gianturco 113, 80143 Naples, Italy., Longo DL; Institute of Biostructures and Bioimaging (IBB), National Research Council of Italy (CNR), Via Nizza 52, 10126 Turin, Italy.
Jazyk:	angličtina
Zdroj:	Metabolites [Metabolites] 2023 Nov 18; Vol. 13 (11). Date of Electronic Publication: 2023 Nov 18.
DOI:	10.3390/metabo13111161
Abstrakt:	Proton transporters play a key role in maintaining the acidic tumor microenvironment; hence, their inhibition has been proposed as a new therapeutic treatment, although few methods can accurately assess their effect in vivo. In this study, we investigated whether MRI-CEST (Magnetic Resonance Imaging-Chemical Exchange Saturation Transfer) tumor pH imaging can be a useful tool to evaluate in vivo the therapeutic efficacy of several Proton Pump Inhibitors (PPIs) in breast cancer. Cell viability and extracellular pH assays were carried out in breast cancer cells cultured at physiological pH (7.4) or acid-adapted (pH of 6.5 and 6.8) following the exposure to inhibitors of V-ATPase (Lansoprazole, Esomeprazole) or NHE1 (Amiloride, Cariporide) at several concentrations. Next, triple-negative breast cancer 4T1 tumor-bearing mice were treated with Lansoprazole or Amiloride and MRI-CEST tumor pH imaging was utilized to assess the in vivo efficacy. Only Lansoprazole induced, in addition to breast cancer cell toxicity, a significant inhibition of proton extrusion. A significant reduction in tumor volume, prolonged survival, and increase in extracellular tumor pH after 1 and 2 weeks were observed after Lansoprazole treatment, whereas no significant changes were detected upon Amiloride treatment. Our results suggested that MRI-CEST tumor pH imaging can monitor the therapeutic efficacy of PPIs in breast cancer murine models. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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