Zimniski S J, Brandt M E, Covey D F, Puett D
Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Florida 33101.
Breast Cancer Res Treat. 1993;26(1):15-21. doi: 10.1007/BF00682696.
The aromatase inhibitor 10-propargylestr-4-ene-3,17-dione (PED) has been evaluated in vivo as an anticancer agent. Prolonged administration of PED to rats bearing dimethylbenzanthracene-induced mammary tumors resulted in significant regression of hormone-responsive tumors within several days. Greater than 50% regression was generally observed after 14 days of treatment, irrespective of dose (1, 5, or 50 mg/kg body weight/day). In addition to tumor regression, a significantly increased incidence in tumor stasis was observed over the course of PED treatment. While all doses of PED examined were equipotent for both tumor regression and stasis, a dose-dependent inhibition of new tumor formation was observed in PED-treated rats. In control animals an average of 1.2 new tumors was observed during the experimental period; in contrast, averages of 0.5 tumors appeared in animals receiving 1 mg PED/kg body weight/day, 0.1 tumors at 5 mg/kg, and at 50 mg of PED/kg body weight/day, no new tumors occurred during the time PED was administered. The effects of PED on both regression of existing tumors and appearance of new tumors were reversed by co-administration of estradiol. Thus, PED impairs estrogen-dependent mammary tumor growth, resulting in cessation of new growth and regression of responsive tumors.
芳香化酶抑制剂10-炔丙基雌甾-4-烯-3,17-二酮（PED）已作为一种抗癌剂进行了体内评估。对携带二甲基苯并蒽诱导的乳腺肿瘤的大鼠长期给予PED，数天内激素反应性肿瘤出现显著消退。无论剂量（1、5或50mg/kg体重/天）如何，治疗14天后通常观察到超过50%的消退。除了肿瘤消退外，在PED治疗过程中观察到肿瘤停滞的发生率显著增加。虽然所检测的所有PED剂量在肿瘤消退和停滞方面效力相同，但在接受PED治疗的大鼠中观察到对新肿瘤形成的剂量依赖性抑制。在对照动物中，实验期间平均观察到1.2个新肿瘤；相比之下，接受1mg PED/kg体重/天的动物平均出现0.5个肿瘤，5mg/kg时为0.1个肿瘤，而在50mg PED/kg体重/天的情况下，在给予PED期间未出现新肿瘤。同时给予雌二醇可逆转PED对现有肿瘤消退和新肿瘤出现的影响。因此，PED损害雌激素依赖性乳腺肿瘤生长，导致新生长停止和反应性肿瘤消退。
