Schneider M R, Michna H, Nishino Y, Neef G, el Etreby M F
Research Laboratories of Schering AG, Berlin, F.R.G.
Anticancer Res. 1990 May-Jun;10(3):683-7.
The progesterone antagonists Onapristone (ZK 98.299) and Mifepristone (RU 486) proved to be strong inhibitors of various rodent mammary tumors. Therefore, a further potent antiprogestin, ZK 112.993, and 11 beta-(4-acetyl-phenyl)-analog of Mifepristone, with a high progesterone receptor affinity was tested in experimental rodent and human breast cancer models. In the hormone-dependent MXT(+) mammary tumor of the mouse, treatment of tumors immediately after implantation with 5 mg/kg for 6 weeks led to an inhibition of growth by 95%, being significantly superior to that caused by tamoxifen, diethylstilbestrol and Onapristone. Treatment of established MXT(+) tumors by ZK 112.993 at doses of 0.5, 1.0 and 2.0 mg/kg led to a strong inhibition that equalled that of ovariectomy and surpassed that of Onapristone in the lower doses. In the human, receptor positive mammary carcinoma T61 implanted in male, castrated nude mice, ZK 112.993 (10 mg/kg) significantly retarded tumor growth. Its effect was again superior to Onapristone though weaker than that of tamoxifen. The NMU-induced mammary carcinoma of the rat (established tumors) was inhibited by ZK 112.993 (5 and 10 mg/kg) in a dose-dependent manner slightly superior to Onapristone but weaker than after ovariectomy. Due to its strong antitumor activity and because of the innovative mechanism of action of antiprogesterones in tumor treatment, ZK 112.993 could be of great value for the treatment of breast cancer.
孕酮拮抗剂奥那司酮（ZK 98.299）和米非司酮（RU 486）被证明是多种啮齿动物乳腺肿瘤的强效抑制剂。因此，在实验性啮齿动物和人类乳腺癌模型中对另一种强效抗孕激素ZK 112.993以及具有高孕酮受体亲和力的米非司酮11β-（4-乙酰苯基）类似物进行了测试。在小鼠激素依赖性MXT（+）乳腺肿瘤中，植入后立即以5 mg/kg的剂量治疗肿瘤6周，导致肿瘤生长抑制率达95%，显著优于他莫昔芬、己烯雌酚和奥那司酮所引起的抑制效果。以0.5、1.0和2.0 mg/kg的剂量用ZK 112.993治疗已形成的MXT（+）肿瘤，导致了强烈的抑制作用，其效果等同于卵巢切除术，且在较低剂量下超过了奥那司酮。在植入雄性去势裸鼠体内的人受体阳性乳腺癌T61中，ZK 112.993（10 mg/kg）显著延缓了肿瘤生长。其效果再次优于奥那司酮，但弱于他莫昔芬。ZK 112.993（5和10 mg/kg）以剂量依赖性方式抑制大鼠NMU诱导的乳腺癌（已形成的肿瘤），其效果略优于奥那司酮，但弱于卵巢切除术后的效果。由于其强大的抗肿瘤活性以及抗孕激素在肿瘤治疗中的创新作用机制，ZK 112.993可能对乳腺癌治疗具有重要价值。
