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Melatonin enhances the inhibitory effect of aminoglutethimide on aromatase activity in MCF-7 human breast cancer cells

机译:褪黑素增强氨基谷氨酰胺对MCF-7人乳腺癌细胞芳香化酶活性的抑制作用

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The inhibition of the aromatase-induced intratumoral estrogen synthesis is one of the main anticancer pharmacological strategies. The aim of this paper was to study if a melatonin pretreatment prior to aminoglutethimide increases the efficiency of the aromatase inhibitor used in treating breast cancer. Aminoglutethimide (100 μM) and melatonin (1 nM) significantly decreased cellular aromatase activity in unpretreated MCF−7 cells. A sequential regimen of melatonin (1 nM) followed 24 h later by aminoglutethimide (100 μM) induced a significantly higher decrease in MCF-7 cell aromatase activity to below the values obtained in unpretreated cells. Melatonin treatment inhibited aromatase mRNA expression in unpretreated cells and a sequential treatment of cells with melatonin followed by aminoglutethimide induced a significant inhibition in the aromatase mRNA expression as compared to cells exposed to the same doses of aminoglutethimide, but without melatonin pretreatment.
机译:抑制芳香化酶诱导的肿瘤内雌激素合成是主要的抗癌药理策略之一。本文的目的是研究在谷氨酰胺预处理之前进行褪黑激素预处理是否能提高芳香酶抑制剂在治疗乳腺癌中的效率。在未经预处理的MCF-7细胞中,氨基谷氨酰胺(100μM)和褪黑激素(1 nM)显着降低了细胞芳香酶的活性。褪黑激素(1 nM)的顺序方案,然后24小时后用氨基谷氨酰胺(100μM)诱导MCF-7细胞芳香化酶活性明显更高的降低,低于未预处理细胞中获得的值。褪黑素处理可抑制未经预处理的细胞中芳香化酶mRNA的表达,相较于暴露于相同剂量但未进行褪黑素预处理的细胞,先用褪黑素再用氨基谷氨酰胺对细胞进行顺序处理可显着抑制芳香化酶mRNA表达。

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