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植物提取物通过 HER2 失活和 JNK 通路抑制 HER2 阳性乳腺癌细胞的上皮-间充质转化并诱导细胞凋亡。

Plant Extract Inhibits Epithelial-Mesenchymal Transition and Induces Apoptosis via HER2 Inactivation and JNK Pathway in HER2-Positive Breast Cancer Cells.

机构信息

College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar.

Biomedical Research Centre, Qatar University, Doha P.O. Box 2713, Qatar.

出版信息

Molecules. 2020 Sep 16;25(18):4240. doi: 10.3390/molecules25184240.

Abstract

() is a medicinal plant used for treating several human diseases in the Middle East. Meanwhile, the outcome of extract on HER2-positive breast cancer remains nascent. Thus, we herein investigated the effects of the aqueous extract obtained from the flowers of on two HER2-positive breast cancer cell lines, SKBR3 and ZR75-1. Our data revealed that extract inhibits cell proliferation and deregulates cell-cycle progression of these two cancer cell lines. extract also prevents the progression of epithelial-mesenchymal transition (EMT), an important event for cancer invasion and metastasis; this is accompanied by upregulations of E-cadherin and β-catenin, in addition to downregulations of vimentin and fascin, which are major markers of EMT. Thus, extract causes a drastic decrease in cell invasion ability of SKBR3 and ZR75-1 cancer cells. Additionally, we found that extract inhibits colony formation of both cell lines in comparison with their matched control. The molecular pathway analysis of HER2 and JNK1/2/3 of extract exposed cells revealed that it can block HER2 and JNK1/2/3 activities, which could be the major molecular pathway behind these events. Our findings implicate that extract may possess chemo-preventive effects against HER2-positive breast cancer via HER2 inactivation and specifically JNK1/2/3 signaling pathways.

摘要

是一种药用植物,用于治疗中东的几种人类疾病。同时, 的提取物对 HER2 阳性乳腺癌的疗效仍处于初期阶段。因此,我们在此研究了从花中获得的 的水提物对两种 HER2 阳性乳腺癌细胞系 SKBR3 和 ZR75-1 的影响。我们的数据显示, 提取物抑制这两种癌细胞系的增殖并使细胞周期进程失调。 提取物还可以阻止上皮-间充质转化(EMT)的发生,这是癌症侵袭和转移的重要事件;这伴随着 E-钙粘蛋白和 β-连环蛋白的上调,以及间充质标志物波形蛋白和 fascin 的下调。因此, 提取物导致 SKBR3 和 ZR75-1 癌细胞的侵袭能力急剧下降。此外,我们发现与相应的对照相比, 提取物抑制了这两种细胞系的集落形成。暴露于 提取物的 HER2 和 JNK1/2/3 的分子途径分析表明,它可以阻断 HER2 和 JNK1/2/3 的活性,这可能是这些事件背后的主要分子途径。我们的研究结果表明, 提取物可能通过 HER2 失活和特定的 JNK1/2/3 信号通路对 HER2 阳性乳腺癌具有化学预防作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef05/7570883/fc6d88b6ea53/molecules-25-04240-g001.jpg

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