Crutchley D J, Conanan L B, Maynard J R
Cancer Res. 1980 Mar;40(3):849-52.
Recent reports suggest that many of the biological effects of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate are mediated via intracellular prostaglandin biosynthesis. We have investigated whether the induction of plasminogen activator by 12-O-tetradecanoylphorbol-13-acetate in cultured HeLa cells is similarly mediated. 12-O-Tetradecanoylphorbol-13-acetate (0.5 to 50 nM) increased intra- and extracellular plasminogen activators and stimulated E- and F-type prostaglandin production. Changes in prostaglandin biosynthesis preceded those in plasminogen activator by several hr. Indomethacin (0.5 microM) abolished prostaglandin production but had no effect on either the magnitude or the time course of induction of plasminogen activator. Similar results were obtained with human skin fibroblasts and MDCK cells. Prostaglandins E1, E2, F2 alpha, and I2 had no direct effect on plasminogen activator in HeLa cells or skin fibroblasts. We conclude that in these cells, phorbol ester independently induces plasminogen activator and prostaglandin biosynthesis.
最近的报告表明,肿瘤启动子十四酰佛波醇-13-乙酸酯的许多生物学效应是通过细胞内前列腺素生物合成介导的。我们研究了十四酰佛波醇-13-乙酸酯在培养的HeLa细胞中诱导纤溶酶原激活剂的过程是否也以类似方式介导。十四酰佛波醇-13-乙酸酯(0.5至50 nM)增加了细胞内和细胞外的纤溶酶原激活剂,并刺激了E型和F型前列腺素的产生。前列腺素生物合成的变化比纤溶酶原激活剂的变化提前数小时。吲哚美辛(0.5 microM)消除了前列腺素的产生,但对纤溶酶原激活剂诱导的幅度或时间进程均无影响。在人皮肤成纤维细胞和MDCK细胞中也获得了类似的结果。前列腺素E1、E2、F2α和I2对HeLa细胞或皮肤成纤维细胞中的纤溶酶原激活剂没有直接影响。我们得出结论,在这些细胞中,佛波酯独立诱导纤溶酶原激活剂和前列腺素生物合成。