| Autor: |
Irrera P; Department of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', 81100 Caserta, Italy.; Institute of Biostructures and Bioimaging (IBB), National Research Council of Italy (CNR), 10126 Turin, Italy., Roberto M; Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy., Consolino L; Department of Nanomedicines and Theranostics, Institute for Experimental Molecular Imaging, RWTH Aachen University, 52074 Aachen, Germany., Anemone A; Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy., Villano D; Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy., Navarro-Tableros V; Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy., Carella A; Institute of Biostructures and Bioimaging (IBB), National Research Council of Italy (CNR), 10126 Turin, Italy., Dastrù W; Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy., Aime S; IRCCS SDN SynLab, 80143 Naples, Italy., Longo DL; Institute of Biostructures and Bioimaging (IBB), National Research Council of Italy (CNR), 10126 Turin, Italy. |
| Abstrakt: |
Novel anticancer treatments target the pH regulating system that plays a major role in tumor progression by creating an acidic microenvironment, although few studies have addressed their effect on tumor acidosis. In this study, we investigated in vivo several proton pump inhibitors (PPIs) targeting NHE-1 (Amiloride and Cariporide) and V-ATPase (Esomeprazole and Lansoprazole) proton transporters in the DU145 androgen-insensitive human prostate cancer model. In cellulo results showed that DU145 are sensitive, with decreasing efficacy, to Amiloride, Esomeprazole and Lansoprazole, with marked cell toxicity both in normoxia and in hypoxia, with almost any change in pH. In vivo studies were performed upon administration of Esomeprazole to assess both the acute and chronic effects, and Iopamidol-based tumor pH imaging was performed to evaluate tumor acidosis. Although statistically significant tumor pH changes were observed a few hours after Esomeprazole administration in both the acute study and up to one week of treatment in the chronic study, longer treatment resulted in a lack of changes in tumor acidosis, which was associated to similar tumor growth curves between treated and control groups in both the subcutaneous and orthotopic models. Overall, this study highlights MRI-CEST tumor pH imaging as a valid approach to monitoring treatment response to PPIs. |
