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氟伐他汀对大鼠乳腺癌发生的预防作用。

Preventive effects of fluvastatin in rat mammary carcinogenesis.

机构信息

Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia.

出版信息

Eur J Cancer Prev. 2013 Jul;22(4):352-7. doi: 10.1097/CEJ.0b013e32835b385d.

Abstract

On the basis of preclinical and clinical evidence, statins lead to risk reduction of several types of neoplasia including breast cancer. This study is the first report on the preventive effects of fluvastatin in experimental breast cancer in vivo. In this experiment, the antineoplastic effects of fluvastatin in the chemoprevention of N-methyl-N-nitrosourea-induced mammary carcinogenesis in female rats were evaluated. The effects of fluvastatin on selected parameters of apoptosis, proliferation, and angiogenesis in mammary tumor cells were determined. The drug was dietary administered at two concentrations of 20 and 200 mg/kg. The experiment was terminated 17 weeks after carcinogen administration; mammary tumors were removed and prepared for histomorphological and immunohistochemical analysis. The basic parameters of experimental carcinogenesis, chosen metabolic variables, and side effects after long-term fluvastatin treatment in animals were assessed. Fluvastatin at higher concentrations suppressed tumor frequency by 63% and tumor incidence by 33% in comparison with the controls. After fluvastatin treatment, immunohistochemical analysis of tumor cells showed a decrease in vascular endothelial growth factor receptor-2 expression by 86% and an increase in caspase-3 by 8.5%. Fluvastatin in both treated groups significantly increased the parameters of serum lipid metabolism and significantly decreased femur compact bone thickness and body weight in animals. Our results suggest that fluvastatin and other statins should be further evaluated for tumor-preventive characteristics.

摘要

基于临床前和临床证据,他汀类药物可降低多种类型的肿瘤风险,包括乳腺癌。本研究是首例关于氟伐他汀在体内实验性乳腺癌预防作用的报告。本实验评估了氟伐他汀在 N-甲基-N-亚硝脲诱导的雌性大鼠乳腺肿瘤发生化学预防中的抗肿瘤作用。测定了氟伐他汀对乳腺肿瘤细胞中凋亡、增殖和血管生成的选定参数的影响。药物以 20 和 200mg/kg 的两种浓度经饮食给药。实验在致癌剂给药 17 周后终止;切除乳腺肿瘤并准备进行组织形态学和免疫组织化学分析。评估了实验致癌的基本参数、选择的代谢变量以及动物长期氟伐他汀治疗后的副作用。与对照组相比,较高浓度的氟伐他汀使肿瘤发生率降低了 63%,肿瘤发生率降低了 33%。氟伐他汀治疗后,肿瘤细胞的免疫组织化学分析显示血管内皮生长因子受体-2 的表达降低了 86%,半胱天冬酶-3 增加了 8.5%。两个治疗组的氟伐他汀均显著改善了血清脂质代谢参数,并显著降低了动物的股骨密质骨厚度和体重。我们的结果表明,氟伐他汀和其他他汀类药物应进一步评估其肿瘤预防特性。

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