Gáti I, Bergström M, Csóka K, Muhr C, Carlsson J
Department of Neurology, Uppsala University, Sweden.
Prostaglandins Leukot Essent Fatty Acids. 1990 Jun;40(2):117-24. doi: 10.1016/0952-3278(90)90153-c.
The effects of two specific 5-lipoxygenase inhibitors AA-863 and U-60,257 (piriprost) on the growth of two human glioma cell lines, U-343 MGa and U-251 MG were investigated. Both monolayer cultured cells and spheroids were studied. The results of the monolayer studies showed potent and dose dependent inhibitory effects on the proliferation of glioma cells (IC50/one week treatment/of AA-863: 9.0 microM, IC50 of U-60,257: 40.0 microM). The experiments made on the tumor spheroids suggested an inhibitory effect on proliferation and volume growth already at lower doses (AA-863: 0.4-2.0 microM, U-60,257: 1.0-5.0 microM), a dose range where effects were not found in monolayers. At higher doses (AA-863: 10.0-30.0 microM, U-60,257: 30.0-90.0 microM) the experiments with spheroids failed to demonstrate a further inhibitory effect on spheroid volume, probably attributed to phenomena such as swelling of cells, dissociation of spheroid structure and development of necrosis. The clearly dose dependent inhibitory effect on the proliferation of human glioma cells in monolayer culture and the inhibitory effects on spheroid growth with these specific inhibitors indicate a role for lipoxygenase products in the growth of gliomas.
研究了两种特异性5-脂氧合酶抑制剂AA-863和U-60,257（吡立前列素）对两种人胶质瘤细胞系U-343 MGa和U-251 MG生长的影响。对单层培养的细胞和球体均进行了研究。单层研究结果显示，对胶质瘤细胞的增殖有强效且剂量依赖性的抑制作用（AA-863一周处理的IC50：9.0微摩尔，U-60,257的IC50：40.0微摩尔）。对肿瘤球体进行的实验表明，在较低剂量（AA-863：0.4 - 2.0微摩尔，U-60,257：1.0 - 5.0微摩尔）时就对增殖和体积生长有抑制作用，而在单层实验中未发现此剂量范围内有效果。在较高剂量（AA-863：10.0 - 30.0微摩尔，U-60,257：30.0 - 90.0微摩尔）时，球体实验未能证明对球体体积有进一步的抑制作用，这可能归因于细胞肿胀、球体结构解离和坏死形成等现象。在单层培养中对人胶质瘤细胞增殖有明显的剂量依赖性抑制作用，以及这些特异性抑制剂对球体生长有抑制作用，表明脂氧合酶产物在胶质瘤生长中起作用。
