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染料木黄酮通过 Hedgehog 通路减少乳腺癌干细胞样细胞群。

Genistein decreases the breast cancer stem-like cell population through Hedgehog pathway.

出版信息

Stem Cell Res Ther. 2013;4(6):146. doi: 10.1186/scrt357.

Abstract

INTRODUCTION

The existence of breast cancer stem-like cells (BCSCs) has profound implications for cancer prevention. Genistein, a predominant isoflavone found in soy products, has multiple robust anti-tumor effects in various cancers, especially in the breast and prostate cancer. In this study, we aimed to evaluate genistein inhibition of BCSCs and its potential mechanism by culturing MCF-7 breast cancer cells and implanting these cells into nude mice.

METHODS

Cell counting, colony formation and cell apoptosis analysis were used to evaluate the effect of genistein on breast cancer cells’ growth, proliferation and apoptosis. We then used mammosphere formation assay and CD44CD24 staining to evaluate the effect of genistein on BCSCs in vitro. A nude mice xenograft model was employed to determine whether genistein could target BCSCs in vivo, as assessed by real-time polymerase chain reaction (PCR) and immunohistochemical staining. The potential mechanism was investigated utilizing real-time PCR, western blotting analysis and immunohistochemical staining.

RESULTS

Genistein inhibited the MCF-7 breast cancer cells’ growth and proliferation and promoted apoptosis. Both in vitro and in vivo genistein decreased breast cancer stem cells, and inhibited breast cancer stem-like cells through down-regulation of the Hedgehog-Gli1 Signaling Pathway.

CONCLUSIONS

We demonstrated for the first time that genistein inhibits BCSCs by down-regulating Hedgehog-Gli1 signaling pathway. These findings provide support and rationale for investigating the clinical application of genistein in treating breast cancer, and specifically by targeting breast cancer stem cells.

摘要

简介

乳腺癌干细胞(BCSCs)的存在对癌症预防具有深远的意义。大豆制品中富含的主要异黄酮染料木黄酮在各种癌症中具有多种强大的抗肿瘤作用,尤其是在乳腺癌和前列腺癌中。在这项研究中,我们旨在通过培养 MCF-7 乳腺癌细胞并将这些细胞植入裸鼠来评估染料木黄酮对 BCSCs 的抑制作用及其潜在机制。

方法

使用细胞计数、集落形成和细胞凋亡分析来评估染料木黄酮对乳腺癌细胞生长、增殖和凋亡的影响。然后,我们使用乳腺球形成测定和 CD44CD24 染色来评估染料木黄酮对体外 BCSCs 的影响。裸鼠异种移植模型用于确定染料木黄酮是否可以在体内靶向 BCSCs,通过实时聚合酶链反应(PCR)和免疫组织化学染色进行评估。利用实时 PCR、western blot 分析和免疫组织化学染色来研究潜在机制。

结果

染料木黄酮抑制 MCF-7 乳腺癌细胞的生长和增殖,并促进细胞凋亡。无论是在体外还是体内,染料木黄酮均降低了乳腺癌干细胞,并通过下调 Hedgehog-Gli1 信号通路抑制了乳腺癌干细胞样细胞。

结论

我们首次证明染料木黄酮通过下调 Hedgehog-Gli1 信号通路抑制 BCSCs。这些发现为研究染料木黄酮在治疗乳腺癌,特别是针对乳腺癌干细胞方面的临床应用提供了支持和依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7565/4054948/34663f7937c2/scrt357-1.jpg

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