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超声通过改变 ABCG2 表达逆转乳腺癌干细胞样细胞的化疗耐药性。

Ultrasound reverses chemoresistance in breast cancer stem cell like cells by altering ABCG2 expression.

机构信息

Ultrasonography Department, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan Province, People's Republic of China

Department of Thyroid Breast and Vascular Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan Province, People's Republic of China.

出版信息

Biosci Rep. 2017 Nov 9;37(6). doi: 10.1042/BSR20171137. Print 2017 Dec 22.

DOI:10.1042/BSR20171137
PMID:28935760
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5678030/
Abstract

Doxorubicin (DOX) resistance in breast cancer largely results from the breast cancer stem cell like cells (BCSCs) which could be targetted to improve the efficacy of chemotherapy. Cell permeabilization using microbubbles (MBs) and ultrasound (US) have the potential for delivering molecules into the cytoplasm. We aim to evaluate a new methodology of US on BCSCs. First, our findings indicated that ALDHA1 spheres which were derived from fresh primary breast cancer samples displayed stem cell like features and were resistant to DOX. In patient cohort, we revealed the presence of a variable fraction of ALDHA1cells in nine out of ten. We, for the first time, showed a new US-MB treatment condition which could be used on ALDHA1 BCSCs by fluorescence measurement and calcein assay. Next, we demonstrated the efficacy of combined treatment on human BCSCs and using DOX and US-MB: the combined treatment with much reduced drug dosage significantly suppressed the stem cell like features of BCSCs and induced BCSCs apoptosis. Furthermore, we suggested that decreased ABCG2 level might be one of the mechanisms by which US-MB medicated DOX treatment. In conclusion, this new US-MB treatment condition has clinical potential in breast cancer therapy by targetting BCSCs; thereby holding benefits for breast cancer patients.

摘要

多柔比星（DOX）耐药性在乳腺癌中主要是由于乳腺癌干细胞样细胞（BCSCs）引起的，这些细胞可以作为靶点来提高化疗的疗效。微泡（MB）和超声（US）的细胞通透性具有将分子递送到细胞质中的潜力。我们旨在评估一种新的超声靶向 BCSCs 的方法。首先，我们的研究结果表明，来源于新鲜原发性乳腺癌样本的 ALDHA1 球体表现出干细胞样特征，并对 DOX 具有耐药性。在患者队列中，我们发现十个中有九个存在可变比例的 ALDHA1 细胞。我们首次展示了一种新的超声-微泡治疗条件，通过荧光测量和钙黄绿素测定可以用于 ALDHA1 BCSCs。接下来，我们使用 DOX 和 US-MB 对人 BCSCs 进行了联合治疗效果的验证：联合治疗用大大减少的药物剂量显著抑制了 BCSCs 的干细胞样特征，并诱导 BCSCs 凋亡。此外，我们提出，ABCG2 水平的降低可能是 US-MB 介导 DOX 治疗的机制之一。总之，这种新的超声-微泡治疗条件通过靶向 BCSCs 具有治疗乳腺癌的临床潜力，从而为乳腺癌患者带来益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbef/5678030/346c13b6e4c9/bsr-37-bsr20171137-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbef/5678030/a46ff6c962cb/bsr-37-bsr20171137-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbef/5678030/b1f643670535/bsr-37-bsr20171137-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbef/5678030/c9e68e5d38e4/bsr-37-bsr20171137-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbef/5678030/7418f9a41a65/bsr-37-bsr20171137-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbef/5678030/346c13b6e4c9/bsr-37-bsr20171137-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbef/5678030/a46ff6c962cb/bsr-37-bsr20171137-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbef/5678030/b1f643670535/bsr-37-bsr20171137-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbef/5678030/c9e68e5d38e4/bsr-37-bsr20171137-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbef/5678030/7418f9a41a65/bsr-37-bsr20171137-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbef/5678030/346c13b6e4c9/bsr-37-bsr20171137-g5.jpg

相似文献

[1]
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引用本文的文献

[1]
Targeting WEE1 Kinase for Breast Cancer Therapeutics: An Update.

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[2]
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J Cell Mol Med. 2025-6

[3]
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J Nanobiotechnology. 2024-6-21

[4]
Stochasticity and Drug Effects in Dynamical Model for Cancer Stem Cells.

Cancers (Basel). 2023-1-21

[5]
Analysis of Factors Affecting 5-ALA Fluorescence Intensity in Visualizing Glial Tumor Cells-Literature Review.

Int J Mol Sci. 2022-1-15

[6]
Cytokines, breast cancer stem cells (BCSCs) and chemoresistance.

Clin Transl Med. 2018-9-3

[7]
Ultrasound microbubbles mediated miR-let-7b delivery into CD133 ovarian cancer stem cells.

Biosci Rep. 2018-9-28

[8]
The SLC34A2-ROS-HIF-1-induced up-regulation of EZH2 expression promotes proliferation and chemo-resistance to apoptosis in colorectal cancer.

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Tumour Biol. 2017-4

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