Gàti I, Bergström M, Westerberg G, Csòka K, Muhr C, Carlsson J
Department of Neurology, Uppsala University, Sweden.
Eur J Cancer. 1990;26(7):802-7. doi: 10.1016/0277-5379(90)90156-n.
Established cell-lines of human glioma origin were cultured as multicellular spheroids or as monolayers. Volume growth and 3H-thymidine labelling were analysed for the spheroids after continuous exposure to drugs interfering with the release of arachidonic acid and the production of prostaglandins and leukotrienes. Comparative measurements were made on monolayer cultures. The cyclo-oxygenase inhibitor indomethacin enhanced growth at intermediate concentrations (0.5-5.0 micrograms/ml) but reduced growth at 50 micrograms/ml. The dual cyclo-oxygenase and lipoxygenase inhibitor ketoprofen had a significant inhibitory effect on growth and cell proliferation of spheroids at high concentration (50 micrograms/ml). The weak lipoxygenase inhibitor NDGA (quinone-form) decreased growth whereas the strong lipoxygenase inhibitor NDGA (hydroquinone-form) did not reduce growth rate but significantly decreased cell proliferation. Quinacrine reduced the spheroid growth rate although dexamethasone had no effects. Thus, inhibitors of the arachidonic acid cascade had growth inhibitory effects in the spheroid tumour model as well as in cells cultured as monolayers.
源自人胶质瘤的已建立细胞系被培养成多细胞球体或单层细胞。在持续暴露于干扰花生四烯酸释放以及前列腺素和白三烯产生的药物后，分析了球体的体积生长和³H-胸腺嘧啶核苷标记情况。对单层培养物进行了对比测量。环氧化酶抑制剂吲哚美辛在中等浓度（0.5 - 5.0微克/毫升）时促进生长，但在50微克/毫升时抑制生长。双环氧化酶和脂氧化酶抑制剂酮洛芬在高浓度（50微克/毫升）时对球体的生长和细胞增殖有显著抑制作用。弱脂氧化酶抑制剂NDGA（醌形式）降低生长，而强脂氧化酶抑制剂NDGA（对苯二酚形式）虽不降低生长速率，但显著降低细胞增殖。奎纳克林降低了球体生长速率，而地塞米松则无作用。因此，花生四烯酸级联反应的抑制剂在球体肿瘤模型以及单层培养的细胞中均具有生长抑制作用。
