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Updated: Apr 4, 2026
Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Carbonic anhydrase IX inhibition is an effective strategy for osteosarcoma treatment
Francesca Perut1, Fabrizio Carta2, Gloria Bonuccelli1
1a 1 Istituto Ortopedico Rizzoli, Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine , via di Barbiano 1/10, 40136 Bologna, Italy +39 05 16 36 66 78 ; +39 05 16 36 68 97 ; francesca.perut@ior.it.
Objective:
Hypoxia-inducible factor 1, a regulator of CA IX activity, is often overexpressed in human osteosarcoma (OS) but not in normal tissues, and its expression levels correlate with prognosis. In this study, we investigated the therapeutic potential of newly synthesized CA IX sulfonamide inhibitors in OS.
Methods:
CA IX expression was evaluated in OS cell lines and bone marrow stromal cells (BMSC). After treatment with CA IX inhibitors, cell proliferation, apoptosis, cell cycle, extracellular and cytosolic pH changes were evaluated both in vitro and in mouse OS xenografts.
Results:
CA IX expression levels were significantly higher in OS than in BMSC. Accordingly, CA IX inhibitor 3 induced remarkable cytotoxicity on OS cells without affecting BMSC proliferation. This activity was increased under hypoxia, and was mediated by cell cycle arrest and by the modulation of cytosolic and extracellular pH. In vivo, CA IX inhibitor 3 reduced tumor growth by inducing significant necrosis.
Conclusions:
Our results provide a strong rationale for the clinical use of the newly synthesized CA IX inhibitor 3 in human OS.
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