Snyder D S, Castro R, Desforges J F
City of Hope National Medical Center, Duarte, California 91010.
Exp Hematol. 1989 Jan;17(1):6-9.
Eicosanoids regulate a wide spectrum of cellular processes including cell proliferation. We have shown previously that lipoxygenase metabolites of arachidonic acid modulate normal human hematopoiesis by in vitro colony assays. In this study we investigated the role of lipoxygenase metabolites in regulating the proliferation of several malignant hematopoietic cell lines, including K562 and EM-2 (chronic myelogenous leukemia blasts), HL-60 (promyelocytic leukemia cells), and U937 (malignant histiocytes). Piriprost, a specific inhibitor of 5-lipoxygenase, inhibits proliferation of these cell lines up to 95% with 50% cell inhibition at approximately 3 x 10(-5) M. Other less specific lipoxygenase inhibitors such as caffeic acid, nordihydroguaiaretic acid, and BW755C have similar activity in a [3H]-thymidine incorporation assay. In contrast, indomethacin, which is a cyclooxygenase inhibitor, has no suppressive effect in these assays. Inhibition by these drugs is completely reversible. Several nonhematopoietic malignant cell lines do not appear to be affected by these drugs. Two specific lipoxygenase metabolites, leukotriene B4 and leukotriene D4, stimulate leukemia cell line proliferation to 150% of control levels when added directly to cell cultures. These data suggest that certain lipoxygenase products, perhaps leukotrienes, are critical for the proliferation of malignant hematopoietic cells in vitro.
类二十烷酸调节包括细胞增殖在内的广泛细胞过程。我们之前已经通过体外集落试验表明，花生四烯酸的脂氧合酶代谢产物可调节正常人的造血作用。在本研究中，我们调查了脂氧合酶代谢产物在调节几种恶性造血细胞系增殖中的作用，这些细胞系包括K562和EM - 2（慢性粒细胞白血病母细胞）、HL - 60（早幼粒细胞白血病细胞）以及U937（恶性组织细胞）。5 - 脂氧合酶的特异性抑制剂哌立前列素在大约3×10⁻⁵ M时可抑制这些细胞系的增殖达95%，50%细胞受到抑制。其他特异性较低的脂氧合酶抑制剂如咖啡酸、去甲二氢愈创木酸和BW755C在[³H] - 胸腺嘧啶核苷掺入试验中具有类似活性。相比之下，环氧化酶抑制剂吲哚美辛在这些试验中没有抑制作用。这些药物的抑制作用是完全可逆的。几种非造血恶性细胞系似乎不受这些药物影响。当直接添加到细胞培养物中时，两种特异性脂氧合酶代谢产物白三烯B4和白三烯D4可将白血病细胞系的增殖刺激至对照水平的150%。这些数据表明，某些脂氧合酶产物，可能是白三烯，对于体外恶性造血细胞的增殖至关重要。
