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白藜芦醇抑制人乳腺癌细胞的迁移和侵袭。

Resveratrol inhibits migration and invasion of human breast-cancer cells.

作者信息

Tang Feng-Yao, Su Yu-Ching, Chen Nai-Chia, Hsieh Hui-Shan, Chen Kaun-Suei

机构信息

Biomedical Science Laboratory, Department of Nutrition, China Medical University, Taichung, Taiwan.

出版信息

Mol Nutr Food Res. 2008 Jun;52(6):683-91. doi: 10.1002/mnfr.200700325.

Abstract

Metastasis is the primary cause of death from breast cancer. Cell migration and invasion play important roles in neoplastic metastasis. The insulin-like growth factor (IGF-1) stimulates cell migration through activation of PI-3K/Akt signaling pathway. IGF-1 induces the tumorigenicity of many types of cancer cells and is critical for metastatic cell spread in estrogen receptor (ER)-negative breast-cancer cells. Matrix metalloproteinase-2 (MMP-2) is a key enzyme in the degradation of extracellular matrices and its expression has been dysregulated in breast cancer invasion and metastasis. Resveratrol exhibited potential anticarcinogenic activities in several studies. However, the inhibitory effects of resveratrol on the expression of MMP-2, migration and invasion of breast-cancer cell have not been demonstrated yet. In the present study, we investigated the anti-invasive mechanism of resveratrol in human breast cancer MDA-MB 435cells. Here, we showed that IGF-1 is a potent stimulant of the migration of ER-negative human breast-cancer cells. Resveratrol could inhibit IGF-1-mediated cell migration of MDA-MB 435 in vitro. The inhibitory effect of resveratrol was mediated in part through the suppression of the activation of PI-3K/Akt signaling pathway. Furthermore, IGF-1-mediated expression of MMP-2 was significantly inhibited by resveratrol in concomitance with alteration of cell invasion.

摘要

转移是乳腺癌致死的主要原因。细胞迁移和侵袭在肿瘤转移中起着重要作用。胰岛素样生长因子(IGF-1)通过激活PI-3K/Akt信号通路刺激细胞迁移。IGF-1诱导多种癌细胞的致瘤性,并且对于雌激素受体(ER)阴性乳腺癌细胞中的转移细胞扩散至关重要。基质金属蛋白酶-2(MMP-2)是细胞外基质降解中的关键酶,其表达在乳腺癌侵袭和转移中已失调。在多项研究中白藜芦醇表现出潜在的抗癌活性。然而,白藜芦醇对MMP-2表达、乳腺癌细胞迁移和侵袭的抑制作用尚未得到证实。在本研究中,我们研究了白藜芦醇在人乳腺癌MDA-MB 435细胞中的抗侵袭机制。在此,我们表明IGF-1是ER阴性人乳腺癌细胞迁移的有效刺激物。白藜芦醇在体外可抑制IGF-1介导的MDA-MB 435细胞迁移。白藜芦醇的抑制作用部分是通过抑制PI-3K/Akt信号通路的激活介导的。此外,白藜芦醇在伴随细胞侵袭改变的同时显著抑制了IGF-1介导的MMP-2表达。

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