唑来膦酸通过抑制外泌体负载的DKK1抑制乳腺癌骨转移

IF 0.9 4区医学 Q4 PHARMACOLOGY & PHARMACY

Bangladesh Journal of Pharmacology Pub Date : 2022-09-07 DOI:10.3329/bjp.v17i3.61292

Bingqing Song, Maozhong Xu, Xiao Fang Xu, Xia Li, Ming Chen

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引用次数: 0

摘要

本研究旨在探讨唑来膦酸在乳腺癌骨转移中的作用机制。Dickkopf 1 (DKK1)在乳腺癌细胞和从乳腺癌细胞分离的外泌体中均有表达。用唑来膦酸或转染cDNA3.1-DKK1可同步抑制乳腺癌细胞和外泌体中DKK1的表达。唑来膦酸处理的MDA-MB-453细胞外泌体显著抑制MDA-MB-453细胞的增殖和迁移，显著抑制破骨细胞的分化和成熟。在RAW264.7细胞与MDA-MB-453细胞共培养系统中，MDA-MB-453细胞衍生的外泌体促进了MDA-MB-453细胞的增殖和迁移。最后，来自唑来膦酸处理的MDA-MB-453细胞的外泌体显著阻断EMT进展和TGF-β信号传导。唑来膦酸通过抑制负载DKK1的外泌体抑制乳腺癌骨转移。

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Zoledronic acid inhibits the bone metastasis of breast cancer by repressing exosome-loaded DKK1

This study is designed to investigate the mechanism underlying zoledronic acid for the bone metastasis of breast cancer. Dickkopf 1 (DKK1) was both expressed in breast cancer cells and exosomes isolated from breast cancer cells. The expression of DKK1 was synchronously inhibited in breast cancer cells and exosomes with zoledronic acid or transfecting with cDNA3.1-DKK1. The proliferation and migration of MDA-MB-453 cells were greatly repressed and the differentiation and maturity of osteoclasts were dramatically repressed by exosomes derived from zoledronic acid-treated MDA-MB-453 cells. In the co-cultural system of RAW264.7 cells and MDA-MB-453 cells, the proliferation and migration of MDA-MB-453 cells were facilitated by exosomes derived from MDA-MB-453 cells. Lastly, the EMT progression and TGF-β signaling were significantly blocked by exosomes derived from zoledronic acid-treated MDA-MB-453 cells. Zoledronic acid suppressed the bone metastasis of breast cancer by inhibiting the exosomes loaded with DKK1.

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来源期刊

Bangladesh Journal of Pharmacology PHARMACOLOGY & PHARMACY-

CiteScore

1.50

自引率

18.80%

发文量

审稿时长

>12 weeks

期刊介绍： Bangladesh Journal of Pharmacology (Bangladesh J Pharmacol) is an open access, video component, peer-reviewed journal of the Bangladesh Pharmacological Society (BDPS). A scholarly publication is defined ''open access'' when there are no financial, legal or technical barriers to accessing it. Anyone can read, download, copy, distribute, print or use it in educational purpose within the legal agreements. Peer review of a manuscript means the evaluation of research work by one or more people with similar competences. It can be open or blind. We do the single-blind peer review. Our readers want to know the methodology used by the researchers which is very important to get the results. The video clip of one of the methodologies is prepared by the authors and submit it to publish.