Kubatka P, Sadlonova V, Kajo K, Nosalova G, Fetisovova Z
Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Sklabinska, Martin, Slovak Republic.
Neoplasma. 2008;55(1):42-6.
Single - agent therapy with aromatase inhibitors has no established role in premenopausal women with breast cancer. In this study, tumor suppressive effects of letrozole in the prevention of N-methyl-N-nitrosourea - induced mammary carcinogenesis in female Sprague-Dawley rats were evaluated. Letrozole was dietary administered in two concentrations - 1 mg/1 kg (LETRO 1), and 10 mg/1 kg (LETRO 10). Letrozole suppressed incidence of mammary gland cancer by 93 % (P<0.00002) in the group LETRO 1 in comparison with control animals. Total suppression of mammary carcinogenesis was observed in the group LETRO 10. In the groups with letrozole, uterine and vaginal atrophy was found at the end of experiment. In letrozole - treated animals in comparison with untreated animals, increased plasmatic triacylglycerol concentrations (P<0.0001) were observed, but total cholesterol and cholesterol of low- and high- density lipoprotein fractions were not significantly changed. An increase in body weight gain and food intake was found in the groups LETRO 1 and LETRO 10 compared with the control group (P<0.0001). The present study points to high tumor suppressive effects of letrozole in premenopausal model of mammary carcinogenesis in female rats.
芳香酶抑制剂单药治疗在绝经前乳腺癌女性中尚未确立其作用。在本研究中，评估了来曲唑在预防N-甲基-N-亚硝基脲诱导的雌性Sprague-Dawley大鼠乳腺癌变中的肿瘤抑制作用。来曲唑以两种浓度经饮食给药——1毫克/1千克（LETRO 1）和10毫克/1千克（LETRO 10）。与对照动物相比，LETRO 1组中来曲唑使乳腺癌发病率降低了93%（P<0.00002）。在LETRO 10组中观察到乳腺癌变完全被抑制。在使用来曲唑的组中，实验结束时发现子宫和阴道萎缩。与未治疗的动物相比，在接受来曲唑治疗的动物中观察到血浆三酰甘油浓度升高（P<0.0001），但总胆固醇以及低密度脂蛋白和高密度脂蛋白部分的胆固醇没有显著变化。与对照组相比，LETRO 1组和LETRO 10组的体重增加和食物摄入量增加（P<0.0001）。本研究表明来曲唑在雌性大鼠绝经前乳腺癌变模型中具有高度的肿瘤抑制作用。
