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European Radiology
Published in: European Radiology 11/2014

01-11-2014 | Ultrasound

Activation of microbubbles by low-level therapeutic ultrasound enhances the antitumor effects of doxorubicin

Authors: Shuang Yang, Pan Wang, Xiaobing Wang, Xiaomin Su, Quanhong Liu

Published in: European Radiology | Issue 11/2014

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Abstract

Objective

To prove that DNA damage, intracellular reactive oxygen species (ROS) generation and loss of mitochondrial membrane potential (MMP) are contributing factors for the inhibition of cell proliferation induced by doxorubicin (DOX) administration combined with microbubble-assisted low-level therapeutic ultrasound (US) in K562 cells.

Methods

3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay was adopted to examine cytotoxicity of different treatments. Changes on apoptosis and necrosis rates, DNA fragmentation, intracellular reactive oxygen species production, mitochondrial membrane potential, cellular membrane permeability and DOX-uptake were analysed by flow cytometry. Nuclear morphology changes were observed under a fluorescence microscope. Ultrasonic cavitation was measured by spectrofluorimetry.

Results

Under optimal conditions, MB-US significantly aggravated DOX-induced K562 cell death, especially necrosis, when compared with either monotherapy. Synergistic potentiation on DNA damage, ROS generation and MMP loss were observed. Ultrasonic cavitation effects, plasma membrane permeabilization and DOX-uptake were notably improved after MB-US exposure.

Conclusions

MB-US could increase the susceptibility of tumours to antineoplastic drugs, suggesting a potential clinical method for US-mediated tumour chemotherapy.

Key Points

• Microbubble-ultrasound (MB-US) aggravated doxorubicin (DOX) induced K562 cell death, especially necrosis
• MB-US synergistically potentiated DOX-initiated DNA damage, ROS generation and MMP loss
• Ultrasonic cavitation effects, plasma membrane permeabilization and DOX-uptake were improved after treatment
• MB-US holds significant potential for improving the efficacy of conventional chemotherapy
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Metadata
Title
Activation of microbubbles by low-level therapeutic ultrasound enhances the antitumor effects of doxorubicin
Authors
Shuang Yang
Pan Wang
Xiaobing Wang
Xiaomin Su
Quanhong Liu
Publication date
01-11-2014
Publisher
Springer Berlin Heidelberg
Published in
European Radiology / Issue 11/2014
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-014-3334-3

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