Combination of Pitavastatin and melatonin shows partial antineoplastic effects in a rat breast carcinoma model
Combination of Pitavastatin and melatonin shows partial antineoplastic effects in a rat breast carcinoma model
复制标题
DOI：
10.1016/j.acthis.2014.09.010
复制
发表时间：
2014-01-01
影响因子：
2.5
通讯作者：
Adamkov, Marian
中科院分区：
文献类型：
--
作者：
Kubatka, Peter;Bojkova, Bianka;Adamkov, Marian
我们以前的研究结果表明，不同的他汀类药物在大鼠乳腺癌发生显着的肿瘤抑制作用。本实验的目的是检查匹伐他汀单独和与松果体激素褪黑激素组合在N-甲基-N-亚硝基脲诱导的雌性Sprague-Dawley大鼠乳腺癌发生模型中的化学预防作用。饮食给予匹伐他汀（10 mg/kg）和水溶液中的褪黑激素（20 μ g/ml）。化学预防在致癌物给药前7天开始，随后持续15周直至尸检。尸检时，切除乳腺肿瘤并准备进行组织病理学和免疫组织化学分析。与对照组相比，匹伐他汀单独使用可使平均肿瘤体积减少58%，潜伏期延长8天;另一方面，该药物使肿瘤发生率增加23%。与对照组相比，匹伐他汀与褪黑激素联合给药使肿瘤发生率降低23%，肿瘤体积降低44%，肿瘤潜伏期延长5.5天。癌细胞的分析显示，在两个处理组中caspase-3表达显著增加，并且在匹伐他汀单独处理后caspase-7表达有增加的趋势。Ki 67在两个治疗组的癌细胞中的表达均显著降低。与对照癌细胞相比，匹伐他汀单独使VEGF表达增加41%，然而褪黑激素完全逆转了其不良作用。匹伐他汀联合褪黑素显著增加动物股骨密质骨厚度。匹伐他汀单独降低血浆甘油三酯和总胆固醇水平，但它显着增加葡萄糖水平。总之，我们的结果显示匹伐他汀联合褪黑素在大鼠乳腺癌模型中具有部分抑制作用。(C)2014 Elsevier GmbH. All rights reserved.
Our previous results indicated significant tumor-suppressive effects of different statins in rat mammary carcinogenesis. The purpose of this experiment was to examine the chemopreventive effects of Pitavastatin alone and in combination with the pineal hormone melatonin in the model of N-methyl-N-nitrosourea-induced mammary carcinogenesis in female Sprague-Dawley rats. Pitavastatin was administered dietary (10 mg/kg) and melatonin in an aqueous solution (20 mu g/ml). Chemoprevention began 7 days prior to carcinogen administration and subsequently continued for 15 weeks until autopsy. At autopsy, mammary tumors were removed and prepared for histopathological and immunohistochemical analysis. Compared to controls, Pitavastatin alone reduced average tumor volume by 58% and lengthened latency by 8 days; on the other hand, the drug increased tumor frequency by 23%. Combined administration of Pitavastatin with melatonin decreased tumor frequency by 23%, tumor volume by 44% and lengthened tumor latency by 5.5 days compared to control animals. The analysis of carcinoma cells showed significant increase in caspase-3 expression in both treated groups and a tendency of increased caspase-7 expression after Pitavastatin treatment alone. Significant expression decrease of Ki67 was found in carcinoma cells from both treated groups. Compared to control carcinoma cells, Pitavastatin alone increased VEGF expression by 41%, however melatonin totally reversed its undesirable effect. Pitavastatin combined with melatonin significantly increased femur compact bone thickness in animals. Pitavastatin alone decreased plasma triglycerides and total cholesterol levels, however it significantly increased levels of glucose. In summary, our results show a partial antineoplastic effect of Pitavastatin combined with melatonin in the rat mammary gland carcinoma model. (C) 2014 Elsevier GmbH. All rights reserved.