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首页> 外文期刊>Cancer Management and Research >Simvastatin Evokes An Unpredicted Antagonism For Tamoxifen In MCF-7 Breast Cancer Cells
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Simvastatin Evokes An Unpredicted Antagonism For Tamoxifen In MCF-7 Breast Cancer Cells

机译：辛伐他汀在MCF-7乳腺癌细胞中唤起了针对他莫昔芬的未预测的拮抗作用

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Purpose: Tamoxifen (TAM) is a non-steroidal antiestrogen drug, used in the prevention and treatment of all stages of hormone-responsive breast cancer. Simvastatin (SIM) is a lipid-lowering agent and has been shown to inhibit cancer cell growth. The study aimed to investigate the effect of the combination of TAM and SIM in the treatment of estrogen receptor positive (ER+) breast cancer cell line, MCF-7, and in mice-bearing Ehrlich solid tumors. Methods: MCF-7 cells were treated with different concentrations of TAM or/and SIM for 72 hours and the effects of the combination treatment on cytotoxicity, oxidative stress markers, apoptosis, angiogenesis, and metastasis were investigated using different techniques. In addition, tumor volume, oxidative markers, and inflammatory markers of the combined therapy were explored in mice bearing solid EAC tumors. Results: The results showed that treatment of MCF-7 cells with the combination of 10 μM TAM, and 2 μM SIM significantly inhibited the increase in oxidative stress markers, LDH, and NF-kB induced by TAM. In addition, there was a significant decrease in the total apoptotic ratio, caspase-3 activity, and glucose uptake, while there was a non-significant change in Bax/bcl-2 ratio compared to the TAM-treated group. Using the isobologram equation, the drug interaction was antagonistic with combination index, CI=1.18. On the other hand, the combination regimen decreased VEGF, and matrix metalloproteinases, MMP 2&9 compared to TAM-treated cells. Additionally, in vivo, the combination regimen resulted in a non-significant decrease in the tumor volume, decreased oxidative markers, and the protein expression of TNF-α, and NF- κ B compared to the TAM treated group. Conclusion: Although the combination regimen of TAM and SIM showed an antagonistic drug interaction in MCF-7 breast cancer, it displayed favorable antiangiogenic, anti-metastatic, and anti-inflammatory effects.
机译：目的：Tamoxifen（TAM）是一种非甾体抗雌激素药物，用于预防和治疗激素响应乳腺癌的所有阶段。辛伐他汀（SIM）是一种脂质降低剂，已被证明抑制癌细胞生长。该研究旨在探讨TAM和SIM组合在雌激素受体阳性（ER +）乳腺癌细胞系，MCF-7和含小鼠EHRLICH实体瘤中的影响。方法：使用不同的技术，用不同浓度的TAM或/和SIM处理MCF-7细胞72小时，并使用不同的技术研究了对细胞毒性，氧化应激标记物，诱导和转移的影响。此外，在携带固体EAC肿瘤的小鼠中探讨了肿瘤体积，氧化标记和炎症标志物的组合治疗。结果：结果表明，用10μmTAM的组合治疗MCF-7细胞，2μmSIM显着抑制TAM诱导的氧化应激标记物，LDH和NF-KB的增加。此外，与TAM处理基团相比，总凋亡比，Caspase-3活性和葡萄糖摄取的总凋亡比和葡萄糖摄取有显着降低，而BAX / BCL-2的比例是非显着的变化。使用异摩尔结构方程，药物相互作用与组合指数拮抗，CI = 1.18。另一方面，与TAM处理的细胞相比，组合方案降低了VEGF和基质金属蛋白酶，MMP 2和9。另外，在体内，组合方案导致肿瘤体积的非显着降低，氧化标记减少，与TNF-α的蛋白表达与TNF-α和NF-κB相比的蛋白质表达与TAM处理的组相比。结论：虽然TAM和SIM的组合方案显示MCF-7乳腺癌中的拮抗药物相互作用，但它显示出有利的抗血管生成，抗转移和抗炎作用。

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