Hilf R, Helton D L
Biochem Pharmacol. 1982 Jan 1;31(1):37-41. doi: 10.1016/0006-2952(82)90232-5.
The effects of estrogens on proline and leucine transport into enzymatically dissociated cells from the R3230AC mammary adenocarcinoma were studied. Estradiol-17beta demonstrated a time- and dose-dependent reduction of proline transport; at 10-6M, transport of proline was decreased by 50 percent. Kinetic analysis of these effects indicate that estradiol displayed characteristics of a non-competitive inhibitor, with a Ki of 1.79 microM. Other estrogens, and the anti-estrogen tamoxifen, gave somewhat higher estimated Ki values and could be ranked as inhibitors as follows estradiol 17beta greater than diethylstilbestrol greater than tamoxifen greater than estriol congruent to estrone greater than estradiol-17alpha. No effects of these estrogens on leucine transport were observed, indicating their selectiveness for the A system. The synthetic glucocorticoid, dexamethasone, was comparable to diethylstilbestrol as an inhibitors of proline transport, but dexamethasone also decreased transport of leucine, Testosterone and progesterone were approximately comparable to estrone in their actions. It is proposed that these actions of estrogens represent one potential mechanism whereby pharmacological levels exert therapeutic benefit in the treatment of advanced breast cancer.
研究了雌激素对R3230AC乳腺腺癌酶解细胞中脯氨酸和亮氨酸转运的影响。17β-雌二醇对脯氨酸转运表现出时间和剂量依赖性的降低；在10^-6M时，脯氨酸转运减少了50%。对这些效应的动力学分析表明，雌二醇表现出非竞争性抑制剂的特征，其抑制常数（Ki）为1.79微摩尔。其他雌激素以及抗雌激素他莫昔芬给出的估计Ki值略高，可按以下顺序列为抑制剂：17β-雌二醇＞己烯雌酚＞他莫昔芬＞雌三醇≡雌酮＞17α-雌二醇。未观察到这些雌激素对亮氨酸转运有影响，表明它们对A系统具有选择性。合成糖皮质激素地塞米松作为脯氨酸转运抑制剂与己烯雌酚相当，但地塞米松也降低了亮氨酸的转运。睾酮和孕酮的作用与雌酮大致相当。有人提出，雌激素的这些作用代表了一种潜在机制，通过该机制，药理水平在晚期乳腺癌治疗中发挥治疗益处。
