Hollingsworth A B, Lerner M R, Lightfoot S A, Wilkerson K B, Hanas J S, McCay P B, Brackett D J
Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Breast Cancer Res Treat. 1998 Jan;47(1):63-70. doi: 10.1023/a:1005872132373.
Leuprolide, a gonadotropin releasing hormone agonist, is currently being evaluated in a pilot study of premenopausal women for the prevention of breast cancer. However, little data is available regarding the efficacy of leuprolide in experimental animal models of carcinoma when administered prior to the carcinogen. In the present study the capacity of leuprolide to prevent tumor development was evaluated by comparing its pretreatment effects in the DMBA-induced rat mammary carcinoma model to pretreatment with tamoxifen and oophorectomy. Fifty-five day old, female Sprague-Dawley rats were randomly allocated to one of four groups: 1) no treatment; 2) oophorectomy two weeks prior to DMBA; 3) leuprolide, 40 microg/kg/day; and 4) tamoxifen, 10 mg/kg/week. All animals received four 5 mg doses of DMBA for a total dose of 20 mg. Leuprolide and tamoxifen treatments began two weeks prior to DMBA and ended one week after DMBA administration. Animals were assessed weekly to determine palpable tumor onset, number, size, and volume. At the conclusion of the study (16 weeks), autopsies were performed and tumor tissue was collected for confirmation of malignancy. Seventy-eight percent of the untreated rats developed tumors. No tumors developed in the oophorectomy group, while the number of rats with tumors was significantly reduced (p<0.05) with both leuprolide (30%) and tamoxifen (21.9%) compared to controls (77.8%). There were no significant differences in the tumor number for each tumor-bearing rat or in tumor volume between treated and control groups. Using our dosage regimen, 'chemical oophorectomy' with leuprolide was not as effective as surgical oophorectomy in the prevention of chemical carcinogenesis by DMBA but was comparable to the results obtained with tamoxifen.
亮丙瑞林是一种促性腺激素释放激素激动剂，目前正在一项针对绝经前女性预防乳腺癌的试点研究中进行评估。然而，关于亮丙瑞林在致癌物给药前用于实验性动物癌模型的疗效，可用数据很少。在本研究中，通过比较亮丙瑞林在二甲基苯并蒽（DMBA）诱导的大鼠乳腺癌模型中的预处理效果与他莫昔芬预处理和卵巢切除术的效果，评估了亮丙瑞林预防肿瘤发生的能力。55日龄的雌性斯普拉格-道利大鼠被随机分为四组之一：1）不治疗；2）在给予DMBA前两周进行卵巢切除术；3）亮丙瑞林，40微克/千克/天；4）他莫昔芬，10毫克/千克/周。所有动物接受4次5毫克剂量的DMBA，总剂量为20毫克。亮丙瑞林和他莫昔芬治疗在给予DMBA前两周开始，并在DMBA给药后一周结束。每周对动物进行评估，以确定可触及肿瘤的发生、数量、大小和体积。在研究结束时（16周），进行尸检并收集肿瘤组织以确认恶性肿瘤。78%的未治疗大鼠发生了肿瘤。卵巢切除组未发生肿瘤，而与对照组（77.8%）相比，亮丙瑞林组（30%）和他莫昔芬组（21.9%）的肿瘤大鼠数量显著减少（p<0.05）。在每个荷瘤大鼠的肿瘤数量或治疗组与对照组之间的肿瘤体积方面，没有显著差异。使用我们的给药方案，亮丙瑞林进行的“化学性卵巢切除”在预防DMBA化学致癌方面不如手术性卵巢切除有效，但与他莫昔芬获得的结果相当。
