Di Monaco M, Brignardello E, Leonardi L, Gatto V, Boccuzzi G
Department of Clinical Pathophysiology, University of Turin, Torino, Italy.
J Cancer Res Clin Oncol. 1995;121(12):710-4. doi: 10.1007/BF01213316.
The antiandrogen flutamide has been reported to exert antiproliferative actions on breast cancer both in vitro and in vivo. Here we study the action of its active metabolite hydroxyflutamide on the oestradiol-induced growth of MCF-7 breast cancer cells. The results show that the antiandrogen inhibits the cell growth. Moreover hydroxyflutamide adds its antiproliferative effect to the action of the antioestrogen tamoxifen. The inhibitory effect is dose-dependent and it is unaffected by tamoxifen concentrations up to levels able to block oestrogen receptors completely. Dihydrotestosterone experiments parallel those on hydroxyflutamide. When the two substances are administered together, neither antagonistic nor additive effects are appreciable. Data are consistent with an androgen-like action of hydroxyflutamide on breast cancer cells. The antiproliferative effect of hydroxyflutamide, without virilizing side-effects, suggests that it is worth exploring its possible employment together with antioestrogens in the treatment of breast cancer patients.
据报道，抗雄激素药物氟他胺在体外和体内均对乳腺癌具有抗增殖作用。在此，我们研究了其活性代谢产物羟基氟他胺对雌二醇诱导的MCF-7乳腺癌细胞生长的作用。结果表明，该抗雄激素药物可抑制细胞生长。此外，羟基氟他胺可增强抗雌激素药物他莫昔芬的抗增殖作用。这种抑制作用呈剂量依赖性，且在他莫昔芬浓度达到完全阻断雌激素受体之前不受其影响。双氢睾酮实验与羟基氟他胺实验结果相似。当这两种物质同时给药时，未观察到拮抗或相加作用。数据表明羟基氟他胺对乳腺癌细胞具有类雄激素样作用。羟基氟他胺的抗增殖作用且无男性化副作用，这表明探索其与抗雌激素药物联合用于治疗乳腺癌患者的可能性是值得的。
