姜黄素通过抑制干细胞样特性和 EMT 对乳腺癌的抗转移活性。

Anti-metastasis activity of curcumin against breast cancer via the inhibition of stem cell-like properties and EMT.

机构信息

School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.

School of Software & Microelectronics, Northwestern Polytechnical University, Xi'an, China.

出版信息

Phytomedicine. 2019 May;58:152740. doi: 10.1016/j.phymed.2018.11.001. Epub 2018 Nov 12.

Abstract

BACKGROUND

Curcumin is a polyphenolic compound with potent chemopreventive and anti-cancer efficacy.

PURPOSE

To explore the potential anti-metastasis efficacy of curcumin in breast cancer stem-like cells (BCSCs), which are increasingly considered to be the origin of the recurrence and metastasis of breast cancer.

METHODS

A CCK8 assay was performed to evaluate cell viability, and a colony formation assay was conducted to determine cell proliferation in MCF-7 and MDA-MB-231 adherent cells. Transwell and wound healing assays were used to detect the effect of curcumin on cell migration and invasion in MDA-MB-231 cells. Mammospheres were cultured with serum free medium (SFM) for three generations and the BCSC surface marker CD44CD24/ subpopulation was measured by flow cytometry. Mammosphere formation and differentiation abilities were determined after cell treatment with curcumin. Then, a reverse transcription-quantitative polymerase chain reaction assay was conducted to detect the relative mRNA level of epithelial-mesenchymal transition (EMT) marker genes and western blot analysis was performed to determine the protein expression of stem cell genes in mammospheres treated with curcumin.

RESULTS

Curcumin exhibited anti-proliferative and colony formation inhibiting activities in both the MCF-7 and MDA-MB-231 cell lines. It also suppressed the migration and invasion of MDA-MB-231 cells. The CD44CD24/ subpopulation was larger in mammospheres when MCF-7 and MDA-MB-231 adherent cells were cultured with SFM. Further studies revealed that curcumin inhibited mammosphere formation and differentiation abilities. Moreover, curcumin down-regulated the mRNA expression of Vimentin, Fibronectin, and β-catenin, and up-regulated E-cadherin mRNA expression levels. Western blot analysis demonstrated that curcumin decreased the protein expression of stem cell genes including Oct4, Nanog and Sox2.

CONCLUSION

The results of the present study suggest that the inhibitor effects of curcumin on breast cancer cells may be related to resistance to cancer stem-like characters and the EMT process. These data indicate that curcumin could function as a type of anti-metastasis agent for breast cancer.

摘要

背景

姜黄素是一种具有强大化学预防和抗癌功效的多酚化合物。

目的

探索姜黄素在乳腺癌干细胞(BCSCs)中的潜在抗转移作用,BCSCs 被认为是乳腺癌复发和转移的起源。

方法

通过 CCK8 检测评估细胞活力,通过集落形成实验检测 MCF-7 和 MDA-MB-231 贴壁细胞的增殖。Transwell 和划痕愈合实验用于检测姜黄素对 MDA-MB-231 细胞迁移和侵袭的影响。在无血清培养基(SFM)中培养三代球体,并通过流式细胞术测量 BCSC 表面标记物 CD44CD24/亚群。用姜黄素处理细胞后,检测球体形成和分化能力。然后,通过逆转录-定量聚合酶链反应检测上皮-间充质转化(EMT)标记基因的相对 mRNA 水平,通过蛋白质印迹分析检测姜黄素处理后球体中的干细胞基因蛋白表达。

结果

姜黄素在 MCF-7 和 MDA-MB-231 细胞系中表现出抗增殖和集落形成抑制活性。它还抑制了 MDA-MB-231 细胞的迁移和侵袭。当 MCF-7 和 MDA-MB-231 贴壁细胞在 SFM 中培养时,球体中的 CD44CD24/亚群更大。进一步的研究表明,姜黄素抑制了球体的形成和分化能力。此外,姜黄素下调了 Vimentin、Fibronectin 和 β-catenin 的 mRNA 表达水平,并上调了 E-cadherin mRNA 表达水平。蛋白质印迹分析表明,姜黄素降低了包括 Oct4、Nanog 和 Sox2 在内的干细胞基因的蛋白表达。

结论

本研究结果表明,姜黄素对乳腺癌细胞的抑制作用可能与抵抗癌症干细胞特征和 EMT 过程有关。这些数据表明,姜黄素可以作为一种抗乳腺癌转移的药物。

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