Antineoplastic drug NSC631570 modulates functions of hypoxic macrophages

• Дата: 2013
• Автори: Skivka, L.M., Fedorchuk, O.G., Rudic, M.P., Pozur, V.V., Khranovska, N.M., Grom, M.Yu., Nowicky, J.W.
• Формат: Стаття
• Мова: English
• Опубліковано: Інститут клітинної біології та генетичної інженерії НАН України 2013
• Назва видання: Цитология и генетика
• Теми: Оригинальные работы
• Онлайн доступ: http://dspace.nbuv.gov.ua/handle/123456789/126597
• Назва журналу: Digital Library of Periodicals of National Academy of Sciences of Ukraine
• Цитувати: Antineoplastic drug NSC631570 modulates functions of hypoxic macrophages / L.M. Skivka, O.G. Fedorchuk, M.P. Rudic, V.V. Pozur, N.M. Khranovska, M.Yu. Grom, J.W. Nowicky // Цитология и генетика. — 2013. — Т. 47, № 5. — С. 70-82. — Бібліогр.: 52 назв. — англ.

Hypoxia is an important factor in the macrophages microenvironment. Many physiological and pathological processes including solid tumor development are characterized by both low oxygen content and presence of macrophages. Tumor-associated hypoxia causes alternative polarization of macrophages in tumor tissue and transformation of these cells into the allies of a malignant neoplasm. The aim of the work was to investigate the effect of NSC631570, a cancerselective drug that is known to selectively accumulate in the tumor tissue, on hypoxic macrophage function. Murine peritoneal macrophages (PMs) were subjected to hypoxia (3% O₂). Nitrite level was assayed by the Griess reaction. Arginase activity was measured by colorimetric method. ROS generation and phagocytosis was estimated by flow cytometry. O₂⁻ generation was assayed by the NBT reduction method. HMGB1 expression was determined by ELISA. 42 h hypoxia caused alternative polarization of murine PMs with significant arginase prevalence. NSC631570 repolarized arginine metabolism of hypoxic macrophages to NOS dominant and activated their pro-inflammatory functions: recovered ROS production and increased alarmin releaseNSC631570 can restore pro-inflammatory functions of macrophages, alternatively polarized by hypoxia.