GROWTH RESPONSE OF GOLDEN HAMSTER EMBRYO CELLS WITH TRANSFORMED PHENOTYPES TO EXOGENOUS ARACHIDONIC ACID

多种生长因子刺激多种细胞中花生四烯酸酯的释放和前列腺素的产生。据报道花生四烯酸和前列腺素都能调节这些生长因子的有丝分裂活性。花生四烯酸可以通过其转化为前列腺素或刺激蛋白激酶C和磷脂酶C等酶的活性来影响细胞生长。在本研究中，我们研究了外源性花生四烯酸对两种金鼠胚胎细胞GHEp38和GHEp69的细胞生长和迁移的影响。在两种细胞的培养基中加入花生四烯酸（10 muM），只刺激表型转化的GHEp69细胞生长。油酸、亚油酸和二十碳五烯酸也能刺激细胞生长，但棕榈酸没有。即使在使用吲哚美辛的情况下也能观察到这种刺激。另一方面，staurosporine是一种蛋白激酶C抑制剂，它可以抑制花生四烯酸刺激细胞生长的作用。这些结果表明，花生四烯酸，而不是前列腺素，通过激活蛋白激酶c来刺激转化的GHE细胞的生长。当使用Boyden室检测花生四烯酸刺激转化的GHE细胞迁移的活性时，花生四烯酸进一步增加了egf刺激的细胞迁移。相比之下，在来源于人胃癌的两种细胞系中，花生四烯酸能有效地刺激细胞迁移，但不能刺激细胞生长。在吲哚美辛存在的情况下，花生四烯酸的这种运动活性被观察到，添加油酸对人癌细胞的迁移没有显著影响。这些结果表明，花生四烯酸对不同类型细胞的生长和运动反应是不同的。阐明各种脂肪酸、前列腺素和白三烯作为第二信使在导致细胞生长和迁移的信号转导中的作用将是重要的。少

A variety of growth factors stimulate the arachidonate release and prostaglandin production in many types of cells. Both arachidonic acid and prostaglandins are reported to modulate mitogenic activity of these growth factors. Arachidonic acid can affect cellular growth through its conversion to prostaglandins or its ability to stimulate activities of enzymes such as protein kinase C and phospholipase C. In this study, we examined the effects of exogenous arachidonic acid on cellular growth and migration in two types of golden hamster embryo cells(GHE), GHEp38 and GHEp69. When arachidonic acid(10 muM) was added in culture medium of both types of cells, only GHEp69 cells with transformed phenotypes were stimulated to grow. Oleic acid, linoleic acid, and eicosapentaenoic acid also stimulated cell growth, but palmitic acid did not. This stimulation was observed even in the presence of indomethacin. On the other hand, staurosporine, an inhibitor of protein kinase C, abolished the action of … More arachidonic acid to stimulate cell growth. These results suggest that arachidonic acid, but not prostaglandins, stimulates growth of transformed GHE cells through the activation of protein kinase C. When arachidonic acid was examined for the activity to stimulate migration of transformed GHE cells using Boyden chamber, arachidonic acid futher increased EGF-stimulated cell migration.In contrast, in two cell lines derived from human gastric carcinomas, arachidonic acid was effective in stimulating cell migration, but not in stimulating cell growth. This motility activity of arachidonic acid was observed in the presence of indomethacin, and addition of oleic acid produced no significant effect on migration of human carcinoma cells. These results indicate that the growth and motility responses induced by arachidonic acid differ in different cell types. It will be important to elucidate roles of various fatty acids, prostaglandins, and leukotrienes as a second messenger in signal transduction leading to cell growth and migration. Less