Mollerup S, Haugen A
Department of Toxicology, National Institute of Occupational Health, Oslo, Norway.
Br J Cancer. 1996 Aug;74(4):613-8. doi: 10.1038/bjc.1996.410.
Polyunsaturated fatty acids (PUFAs) have been implicated in tumour development and have been shown to influence cell proliferation in vitro. We report here that n-3 and n-6 PUFAs at concentration > 10 microM inhibited the proliferation of a human kidney epithelial cell line (21HKE), which has retained phenotypic characteristics of normal kidney epithelial cells. In contrast, the proliferation was stimulated by n-3 and n-6 PUFAs at concentrations < 10 microM under defined growth conditions. The stimulatory effect of n-3 and n-6 PUFAs was even more profound in the presence of EGF. In human kidney epithelial cell lines reflecting different stages of transformation (11HKE and 1THKEras), the stimulatory effect was abrogated both in the presence and absence of EGF. Saturated fatty acids did not show any stimulatory effect on cell growth. The tyrosine kinase inhibitors genistein and tyrphostin-47 inhibited EGF-induced protein tyrosine phosphorylation dose-dependently in the 21HKE cells, and abolished the growth stimulatory effect of docosahexaenoic acid (DHA). This indicates the involvement of EGF receptor tyrosine kinase activity in the observed increase in cell proliferation.
多不饱和脂肪酸（PUFAs）与肿瘤发展有关，并且已显示在体外会影响细胞增殖。我们在此报告，浓度大于10微摩尔的n-3和n-6多不饱和脂肪酸抑制了人肾上皮细胞系（21HKE）的增殖，该细胞系保留了正常肾上皮细胞的表型特征。相反，在特定生长条件下，浓度小于10微摩尔的n-3和n-6多不饱和脂肪酸会刺激细胞增殖。在表皮生长因子（EGF）存在的情况下，n-3和n-6多不饱和脂肪酸的刺激作用更为显著。在反映不同转化阶段的人肾上皮细胞系（11HKE和1THKEras）中，无论有无EGF，刺激作用均被消除。饱和脂肪酸对细胞生长未显示出任何刺激作用。酪氨酸激酶抑制剂染料木黄酮和 tyrphostin-47 在 21HKE 细胞中剂量依赖性地抑制 EGF 诱导的蛋白酪氨酸磷酸化，并消除了二十二碳六烯酸（DHA）的生长刺激作用。这表明表皮生长因子受体酪氨酸激酶活性参与了所观察到的细胞增殖增加。
