Anti-metastasis activity of curcumin against breast cancer via the inhibition of stem cell-like properties and EMT
Anti-metastasis activity of curcumin against breast cancer via the inhibition of stem cell-like properties and EMT
复制标题
姜黄素通过抑制干细胞样特性和 EMT 发挥抗乳腺癌转移活性
DOI：
10.1016/j.phymed.2018.11.001
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发表时间：
2019-05-01
期刊：
影响因子：
7.9
通讯作者：
Wang Hongqi
中科院分区：
文献类型：
--
作者：
Hu Chenxia;Li Mengjie;Wang Hongqi
背景：姜黄素是一种具有很强的化学预防和抗癌作用的多酚化合物。目的：探讨姜黄素对乳腺癌干细胞的潜在抗转移作用。方法：采用CCK8法检测细胞活性，克隆形成实验检测MCF-7和MDA-MB-231细胞的增殖。用Transwell和创面愈合实验检测姜黄素对MDA-MB-231细胞迁移和侵袭的影响。无血清培养3代，流式细胞仪检测BCSC表面标志CD44(+)、CD24(-)/(Low)亚群。用姜黄素处理细胞后，测定乳腺小球的形成和分化能力。结果：姜黄素对MCF-7和MDA-MB-231细胞均具有抗增殖和抑制集落形成的作用。并能抑制MDA-MB-231细胞的迁移和侵袭。当MCF-7和MDA-MB-231贴壁细胞与SFM共同培养时，乳腺CD44(+)CD24(-)/(低)亚群较多。进一步的研究表明，姜黄素抑制乳腺小球的形成和分化能力。此外，姜黄素下调Vimentin、FN和β-catenin的mRNA表达，上调E-cadherin的mRNA表达水平。Western印迹分析显示，姜黄素降低了Oct4、Nanog和Sox2等干细胞基因的蛋白表达。结论：姜黄素对乳腺癌细胞的抑制作用可能与其对肿瘤干细胞样特性的抵抗和EMT过程有关。这些数据表明，姜黄素可以作为一种乳腺癌的抗转移药物。
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 CD44(+)CD24(-)/(low) 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 CD44(+)CD24(-)/(low) 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 beta-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.