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首页> 外文期刊>Cellular Physiology and Biochemistry >The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice
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The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice

机译：化学预防性多酚姜黄素可预防免疫缺陷小鼠的血源性乳腺癌转移

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Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitro and in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA- MB- 231 cells in correlation with reduced activation of the survival pathway NF kappa B, as a consequence of diminished I kappa B and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NF kappa B activity and transcriptional downregulation of AP-1. NF kappa B/p65 silencing is sufficient to downregulate c-jun and MMP expression. Reduced NF kappa B/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NF kappa B/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible. Copyright (c) 2007 S. Karger AG, Basel.
机译：转移细胞的传播可能在诊断原发性肿瘤之前很久就发生了。因此，高危患者在癌变早期阶段的转移是潜在的预防目标。已经提出植物多酚姜黄素用于饮食上的癌症预防。因此，我们在体外和小鼠转移模型中研究了其对人乳腺癌细胞系MDA-MB-231的影响。由于IκB减少和p65磷酸化的结果，姜黄素强烈诱导MDA-MB-231细胞凋亡，与存活途径NFκB的活化减少有关。姜黄素还由于NFκB活性降低和AP-1的转录下调而降低了主要基质金属蛋白酶（MMP）的表达。 NFκB / p65沉默足以下调c-jun和MMP表达。心内注射231细胞后，免疫缺陷小鼠的NFκB/ AP-1活性和MMP表达降低，导致通过重组基底膜的侵袭减少，并且肺转移的数量明显减少（p = 0.0035）。经姜黄素治疗的动物中有68％，但未治疗的动物中只有17％没有或仅有很少的肺转移，这很可能是由于NFκB/ AP-1依赖性MMP表达下调和对循环肿瘤细胞的直接凋亡作用所致。在确定的转移上。因此饮食的化学预防转移似乎是可行的。版权所有（c）2007 S.Karger AG，巴塞尔。

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