Zaccheo T, Giudici D, di Salle E
Experimental Endocrinology, Research/Oncology, Pharmacia and Upjohn, Nerviano (MI), Italy.
J Steroid Biochem Mol Biol. 1998 Feb;64(3-4):193-8. doi: 10.1016/s0960-0760(97)00157-x.
PNU 157706 [N-(1,1,1,3,3,3-hexafluorophenylpropyl)-3-oxo-4-aza-5alpha-androst-1-ene-17beta-carboxamide] is a novel, potent and selective dual 5alpha-reductase inhibitor. We have investigated its effect on tumor growth, endocrine organ weights and prostatic dihydrotestosterone (DHT) content in rats bearing the androgen dependent Dunning R3327 prostatic carcinoma. Animals with tumor diameters of about 1 cm were treated orally for 9 weeks with PNU 157706 (2 and 10 mg/kg/day, 6 days a week) or they were castrated, to check the hormone responsiveness of the tumor. PNU 157706 was effective at both doses tested in reducing tumor growth (53 and 51% inhibition at 2 and 10 mg/kg/day, respectively), while castration caused higher inhibition (82%) of tumor growth. A marked reduction of ventral prostate weight occurred in rats treated with both doses of PNU 157706 (75 and 78%) or castrated (91%). Seminal vesicle weight was also reduced by PNU 157706 administration (56 and 61% inhibition), whereas testes, adrenal, thymus and pituitary weights were not affected. Prostatic DHT content was markedly suppressed (85 and 91%) in PNU 157706 treated rats, compared to 95% suppression caused by castration. These data support a possible role of dual 5alpha-reductase inhibitors in the hormonal therapy of prostatic cancer.
PNU 157706 [N-(1,1,1,3,3,3-六氟苯基丙基)-3-氧代-4-氮杂-5α-雄甾-1-烯-17β-甲酰胺]是一种新型、强效且具有选择性的双5α-还原酶抑制剂。我们研究了其对携带雄激素依赖性邓宁R3327前列腺癌的大鼠肿瘤生长、内分泌器官重量及前列腺二氢睾酮（DHT）含量的影响。肿瘤直径约1厘米的动物口服PNU 157706（2和10毫克/千克/天，每周6天）治疗9周，或者进行去势手术，以检查肿瘤的激素反应性。PNU 157706在两个测试剂量下均有效抑制肿瘤生长（2和10毫克/千克/天分别抑制53%和51%），而去势导致更高的肿瘤生长抑制率（82%）。两种剂量的PNU 157706治疗的大鼠（抑制率分别为75%和78%）或去势大鼠（抑制率为91%）的腹侧前列腺重量均显著降低。给予PNU 157706也使精囊重量降低（抑制率分别为56%和61%），而睾丸、肾上腺、胸腺和垂体重量未受影响。与去势导致95%的抑制率相比，PNU 157706治疗的大鼠前列腺DHT含量显著降低（85%和91%）。这些数据支持双5α-还原酶抑制剂在前列腺癌激素治疗中可能发挥的作用。
