Ganoderma lucidum extract (GLE) impairs breast cancer stem cells by targeting the STAT3 pathway.
Ganoderma lucidum extract (GLE) impairs breast cancer stem cells by targeting the STAT3 pathway.
复制标题
DOI：
10.18632/oncotarget.26294
复制
发表时间：
2018-11-13
期刊：
影响因子：
--
通讯作者：
Martinez-Montemayor, Michelle M
中科院分区：
文献类型：
--
作者：
Rios-Fuller, Tiffany J;Ortiz-Soto, Gabriela;Martinez-Montemayor, Michelle M
三阴性乳腺癌(TNBC)的侵袭性可能部分是由于乳腺癌干细胞(BCSCs)的存在，BCSCs是参与肿瘤发生、发展、转移、复发和治疗耐药的一种细胞亚群。信号转导和转录激活因子3(STAT3)通路参与了BCSCs的发生和发展，但其在TNBC中的作用尚不清楚。在此，我们报道了灵芝提取物(GLE)，一种具有抗癌活性的药用蘑菇，通过下调STAT3通路，在体外和TNBC临床前动物模型中作用于BCSCs。我们发现GLE显著降低了TNBC细胞的活力，并下调了总的和磷酸化的STAT3的表达。这与OCT4、NANOG和SOX2表达的减少、ALDH1和CD44+/CD24-群体的丧失导致BCSC群体的减少、乳房的变形以及动物肿瘤体积和肿瘤重量的显著减少是一致的。对肿瘤中BCSC的分析表明，GLE降低了BCSC中STAT3途径和OCT4、NANOG和SOX2的表达。这些发现表明，GLE的抗癌活性是通过下调STAT3途径来靶向TNBC的BCSCs。
The aggressive nature of triple negative breast cancer (TNBC) may be explained in part by the presence of breast cancer stem cells (BCSCs), a subpopulation of cells, which are involved in tumor initiation, progression, metastasis, recurrence, and therapy resistance. The signal transducer and activator of transcription 3 (STAT3) pathway participates in the development and progression of BCSCs, but its role in TNBC remains unclear. Here, we report that Ganoderma lucidum extract (GLE), a medicinal mushroom with anticancer activity, acts on BCSCs in vitro and in TNBC pre-clinical animal tumor models by downregulating the STAT3 pathway. We show that GLE significantly reduces TNBC cell viability, and down-regulates total and phosphorylated STAT3 expression. This is consistent with the reduction of OCT4, NANOG and SOX2 expression, reduction in the BCSC population by loss of the ALDH1 and CD44+/CD24- population, the deformation of mammospheres, and the strong reduction in animal tumor volume and tumor weight. Analysis of the BCSC compartment in tumors revealed that GLE decreases the STAT3 pathway and the expression of OCT4, NANOG, and SOX2 in BCSCs. These findings demonstrate that the anti-cancer activity of GLE targets BCSCs of TNBC through the downregulation of the STAT3 pathway.