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姜黄素通过上皮-间质转化抑制乳腺癌细胞系的侵袭能力。

Curcumin inhibits invasive capabilities through epithelial mesenchymal transition in breast cancer cell lines.

作者信息

Gallardo Marcela, Calaf Gloria M

机构信息

Instituto de Alta Investigación, Universidad de Tarapacá, Arica, Chile.

出版信息

Int J Oncol. 2016 Sep;49(3):1019-27. doi: 10.3892/ijo.2016.3598. Epub 2016 Jul 4.

Abstract

Curcumin (diferuloyl methane) is an antioxidant that exerts antiproliferative and apoptotic effects and has anti-invasive and anti-metastatic properties. Evidence strongly implicates that epithelial-mesenchymal transition (EMT) is involved in malignant progression affecting genes such as Slug, AXL and Twist1. These genes are abnormally expressed in many tumors and favor metastasis. The purpose of this study was to determine the potential effect of curcumin on EMT, migration and invasion. Triple-positive and triple-negative breast cancer cell lines for estrogen receptor (ER), progesterone receptor (PgR) and HER/neu were used: i) MCF-10F, a normal immortalized breast epithelial cell line (negative), ii) Tumor2, a malignant and tumorigenic cell line (positive) derived from Alpha5 cell line injected into the immunologically depressed mice and transformed by 60/60 cGy doses of high LET (linear energy transfer) α particles (150 keV/µm) of radiation and estrogen, and iii) a commercially available MDA-MB‑231 (negative). The effect of curcumin (30 µM for 48 h) was evaluated on expression of EMT-related genes by RT-qPCR. Results showed that curcumin decreased E-cadherin, N-cadherin, β-catenin, Slug, AXL, Twist1, Vimentin and Fibronectin protein expression, independently of the positivity of the markers in the cell lines. Curcumin also decreased migration and invasive capabilities in comparison to their own controls. It can be concluded that curcumin influenced biochemical changes associated with EMT-related genes that seems to promote such transition and are at the core of several signaling pathways that mediate the transition. Thus, it can be suggested that curcumin is able to prevent or delay cancer progression through the interruption of this process.

摘要

姜黄素(二阿魏酰甲烷)是一种抗氧化剂,具有抗增殖和凋亡作用,并具有抗侵袭和抗转移特性。有充分证据表明,上皮-间质转化(EMT)参与了影响Slug、AXL和Twist1等基因的恶性进展。这些基因在许多肿瘤中异常表达并促进转移。本研究的目的是确定姜黄素对EMT、迁移和侵袭的潜在影响。使用了雌激素受体(ER)、孕激素受体(PgR)和HER/neu三阳性和三阴性乳腺癌细胞系:i)MCF-10F,一种正常的永生化乳腺上皮细胞系(阴性);ii)Tumor2,一种恶性致瘤细胞系(阳性),它由注射到免疫抑制小鼠体内的Alpha5细胞系衍生而来,并经60/60 cGy剂量的高传能线密度(LET)α粒子(150 keV/µm)辐射和雌激素转化;iii)市售的MDA-MB-231(阴性)。通过RT-qPCR评估姜黄素(30 µM,作用48小时)对EMT相关基因表达的影响。结果表明,姜黄素降低了E-钙黏蛋白、N-钙黏蛋白、β-连环蛋白、Slug、AXL、Twist1、波形蛋白和纤连蛋白的蛋白表达,与细胞系中标志物的阳性情况无关。与各自的对照相比,姜黄素还降低了迁移和侵袭能力。可以得出结论,姜黄素影响了与EMT相关基因有关的生化变化,这些基因似乎促进了这种转化,并且是介导该转化的几种信号通路的核心。因此,可以认为姜黄素能够通过中断这一过程来预防或延缓癌症进展。

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