Pinski J, Halmos G, Shirahige Y, Wittliff J L, Schally A V
Endocrine, Polypeptide and Cancer Institute, Veterans Administration Medical Center, New Orleans, Louisiana 70146.
J Clin Endocrinol Metab. 1993 Nov;77(5):1388-92. doi: 10.1210/jcem.77.5.8077338.
Treatment of nude mice bearing xenografts of the human malignant glioma U87MG cell line with the steroid hormone antagonist RU486 for 4 weeks resulted in a significant and dose-dependent suppression of tumor volume and weight. Receptor analyses of tumor cytosol preparations demonstrated a single class of high affinity binding sites for dexamethasone, but the absence of receptors for progesterone. RU486 also nullified the stimulatory effect of dexamethasone on proliferation of U87MG cells in vitro. These results indicate that the growth of U87MG human malignant glioma is dependent on corticoids. The antiproliferative effect of RU486 appears to be due to the inhibition of binding of glucocorticoid hormones to their receptor proteins. Our results suggest a new therapy for some brain tumors, such as malignant gliomas based on the steroid hormone antagonist RU486.
用甾体激素拮抗剂RU486对携带人恶性胶质瘤U87MG细胞系异种移植瘤的裸鼠进行为期4周的治疗,可显著且剂量依赖性地抑制肿瘤体积和重量。肿瘤胞质溶胶制剂的受体分析显示存在一类地塞米松高亲和力结合位点,但不存在孕酮受体。RU486还消除了地塞米松对U87MG细胞体外增殖的刺激作用。这些结果表明,U87MG人恶性胶质瘤的生长依赖于皮质类固醇。RU486的抗增殖作用似乎是由于抑制了糖皮质激素与其受体蛋白的结合。我们的结果提示了一种基于甾体激素拮抗剂RU486的针对某些脑肿瘤如恶性胶质瘤的新疗法。