Croxtall J D, Emmas C, White J O, Choudhary Q, Flower R J
Department of Biochemical Pharmacology, William Harvey Research Institute, Medical College of St Bartholomews Hospital, London, U.K.
Biochem Pharmacol. 1994 Jan 20;47(2):197-202. doi: 10.1016/0006-2952(94)90006-x.
The non-steroidal anti-oestrogen tamoxifen inhibits proliferation of the A549 human lung adenocarcinoma cell line (EC50 congruent to 10 nM) yet there was no evidence of oestrogen receptor expression as determined by ligand binding assay and northern blotting. 17-beta-Oestradiol had no effect on A549 cell proliferation (1 pM-1 microM) and moreover a 100-fold excess failed to reverse the effect of 10 nM tamoxifen as did a 100-fold excess of the steroidal anti-oestrogens ICI 164384 and ICI 182780. However, 4-hydroxytamoxifen which had no significant effect on A549 cell growth (1 pM-1 microM) completely antagonized the effect of 10 nM tamoxifen when used at a 100-fold excess. In the presence of oleic acid and stearic acid (10 microM) the growth inhibitory effect of tamoxifen in A549 cells was greatly enhanced, unlike effects mediated by the anti-oestrogen binding protein described in other cells where these fatty acids had no effect. These results indicate the presence of a unique and highly sensitive mechanism in A549 cells whereby concentrations of tamoxifen relevant to classical receptor binding can inhibit cell growth in the absence of the oestrogen receptor.
非甾体类抗雌激素他莫昔芬可抑制A549人肺腺癌细胞系的增殖（半数有效浓度约为10 nM），然而，通过配体结合试验和Northern印迹法测定，未发现雌激素受体表达的证据。17-β-雌二醇对A549细胞增殖无影响（1 pM - 1 μM），此外，100倍过量的17-β-雌二醇不能逆转10 nM他莫昔芬的作用，甾体类抗雌激素ICI 164384和ICI 182780的100倍过量也不能逆转其作用。然而，对A549细胞生长无显著影响（1 pM - 1 μM）的4-羟基他莫昔芬在100倍过量使用时可完全拮抗10 nM他莫昔芬的作用。在油酸和硬脂酸（10 μM）存在的情况下，他莫昔芬对A549细胞的生长抑制作用大大增强，这与其他细胞中抗雌激素结合蛋白介导的作用不同，在其他细胞中这些脂肪酸没有作用。这些结果表明，A549细胞中存在一种独特且高度敏感的机制，即与经典受体结合相关的他莫昔芬浓度在没有雌激素受体的情况下也能抑制细胞生长。
