Use of Arsenic Trioxide as an Antivascular and Thermosensitizing Agent in Solid Tumors

• Published in: Neoplasia (New York, N.Y.) N.Y.), 2000, Vol.2 (6), p.555-560
• Main Authors: Griffin, Robert J., Lee, Sang H., Rood, Kelly L., Stewart, Michael J., Lyons, John C., Lew, Young S., Park, Heonjoo, Song, Chang W.
• Format: Article
• Language: English
• Subjects: adhesion molecules; Angiogenesis Inhibitors - therapeutic use; Animals; Antineoplastic Agents - therapeutic use; Arsenic Trioxide; Arsenicals - therapeutic use; E-Selectin - metabolism; Female; Fibrosarcoma - blood supply; Fibrosarcoma - pathology; Fibrosarcoma - therapy; Hyperthermia, Induced; Immunohistochemistry; Intercellular Adhesion Molecule-1 - metabolism; Male; Mammary Neoplasms, Experimental - blood supply; Mammary Neoplasms, Experimental - pathology; Mammary Neoplasms, Experimental - therapy; Mice; Mice, Inbred A; Mice, Inbred C3H; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - metabolism; Oxides - therapeutic use; thermosensitization; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - metabolism; tumor perfusion; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 1476-5586; 1522-8002; 1476-5586; 1522-8002
• DOI: 10.1038/sj.neo.7900123

Arsenic trioxide, As2O3 (ATO), has been found to be an effective chemotherapy drug for acute promyelocytic leukemia but its effect on solid tumors has not been fully explored. In the present report, we describe our observation that ATO is a potent antivascular agent and that it markedly enhances the effect of hyperthermia on tumors. The tumor blood perfusion in SCK tumors of A/J mice and FSall tumors of C3H mice was significantly suppressed for up to 24 hours after an i.p. injection of 8 mg/kg ATO. ATO was also found to be able to increase the thermosensitivity of tumor cells in vitro. As a probable consequence of these effects, ATO treatment markedly increased the tumor growth delay caused by hyperthermia at 41.5-42.5°C. Immunohistochemical staining of tumor tissue revealed that the expression levels of several adhesion molecules and TNFa are noticeably increased in tumors 2–6 hours after systemic ATO treatment. It is concluded that ATO is potentially useful to enhance the effect of hyperthermia on tumors at a clinically relevant temperature.