Stem Cell Research & Therapy, 2013, 4(6):5614-5624.

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

Panhong Fan, Shujun Fan, Huan Wang, et al

Department of Pathology Dalian Medical University Dalian P.R. China; The Key Laboratory of Tumor Stem Cell Research of Liaoning Province Dalian Medical University Dalian P.R. China; Department of Pathology Thomas Jefferson University Hospital Philadelphia, USA

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.

英国《干细胞研究与治疗》，2013年6月

金雀异黄素通过Hedgehog途径降低乳腺癌癌症干细胞的数量

范攀红，范淑君，王焕，等

中国大连医科大学病理学院；中国辽宁省大连医科大学肿瘤干细胞研究重点实验室；美国费城托马斯杰斐逊医科大学病理学院

摘要

简介︰

乳腺癌干细胞样细胞 （BCSCs） 的存在对预防癌症具有深远的影响。金雀异黄素，一种大豆产物中被发现的主要异黄酮，对各种癌症具有多种强健的抗肿瘤效果，尤其是乳腺癌和前列腺癌。在此研究中，我们旨在通过培养 MCF-7 乳腺癌细胞并将这些细胞植入到裸鼠体内来评价金雀异黄素抑制BCSCs及其潜在的机制。

方法︰

细胞计数、 群落形成和细胞凋亡分析被用来评价金雀异黄素对乳腺癌细胞的生长、 增殖和凋亡的影响。然后我们使用乳腺球群细胞形成法和 CD44CD24 染色法来评价金雀异黄素对体外BCSCs的影响。用实时聚合酶链反应 (PCR) 和免疫组化染色法评估，裸鼠异种移植模型被用来确定金雀异黄素是否可以靶向体内BCSCs。利用实时 PCR，免疫印迹法和免疫组织化学染色来探究潜在的机理。

结果︰

金雀异黄素抑制 MCF-7 乳腺癌细胞的生长和增殖，并促进细胞凋亡。在体内和体外，金雀异黄素通过下调的Hedgehog-Gli1 信号通路，降低乳腺癌干细胞，并抑制乳腺癌肿瘤干细胞样细胞。

结论︰

我们第一次证明，金雀异黄素通过下调Hedgehog-Gli1信号通路抑制了BCSCS。这些研究结果为探究金雀异黄素治疗乳腺癌，特别是靶向乳腺癌干细胞的临床应用提供了支持和理论基础。