Genistein decreases the breast cancer stem-like cell population through Hedgehog pathway.
Genistein decreases the breast cancer stem-like cell population through Hedgehog pathway.
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DOI：
10.1186/scrt357
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发表时间：
2013
影响因子：
7.5
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Fan P;Fan S;Wang H;Mao J;Shi Y;Ibrahim MM;Ma W;Yu X;Hou Z;Wang B;Li L
乳腺癌干细胞样细胞（BCSC）的存在对癌症预防具有深远的影响。金雀异黄酮是豆制品中发现的一种主要异黄酮，对多种癌症（尤其是乳腺癌和前列腺癌）具有多种强大的抗肿瘤作用。在本研究中，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体内来评估金雀异黄酮对BCSCs的抑制作用及其潜在机制。通过细胞计数、集落形成和细胞凋亡分析来评估金雀异黄素对乳腺癌细胞生长、增殖和凋亡的影响。然后，我们使用乳腺球形成测定和 CD44CD24 染色来评估金雀异黄素对体外 BCSC 的影响。采用裸鼠异种移植模型来确定金雀异黄素是否可以体内靶向 BCSC，并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、蛋白质印迹分析和免疫组织化学染色研究了潜在机制。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。在体外和体内金雀异黄素均能减少乳腺癌干细胞，并通过下调 Hedgehog-Gli1 信号通路抑制乳腺癌干细胞样细胞。我们首次证明金雀异黄素通过下调 Hedgehog-Gli1 信号通路来抑制 BCSC。这些发现为研究金雀异黄素在治疗乳腺癌中的临床应用（特别是针对乳腺癌干细胞）提供了支持和理论依据。
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. 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. 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. 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.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
DOI：
10.1158/1078-0432.ccr-09-2937
发表时间：
2010-05-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Li Y;Zhang T;Korkaya H;Liu S;Lee HF;Newman B;Yu Y;Clouthier SG;Schwartz SJ;Wicha MS;Sun D
通讯作者：
Sun D
Sonic Hedgehog 通路对于维持人类胃癌中的癌症干细胞样细胞至关重要。
影响因子：
3.7
作者：
Song Z;Yue W;Wei B;Wang N;Li T;Guan L;Shi S;Zeng Q;Pei X;Chen L
通讯作者：
Chen L
影响因子：
8
作者：
Wang, X.;Venugopal, C.;Singh, S. K.
通讯作者：
Singh, S. K.
乳腺干细胞、自我更新途径和致癌作用。
影响因子：
7.4
作者：
Liu, SL;Dontu, G;Wicha, MS
通讯作者：
Wicha, MS