Low-intensity pulsed ultrasound affects proliferation and migration of human hepatocellular carcinoma cells

Abstract Purpose Low-intensity pulsed ultrasound (LIPUS) is an effective ancillary treatment modality for various malignancies. However, the mechanisms underlying the role of LIPUS in cancer treatment have not been fully elucidated. We investigated the effects and underlying mechanism of LIPUS on th...

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Main Authors: Mingzhen Yang, Zhihui Lu, Bangzhong Liu, Guanghua Liu, Mingfang Shi, Ping Wang
Format: Article
Language:English
Published: Springer 2025-04-01
Series:Journal of Cancer Research and Clinical Oncology
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Online Access:https://doi.org/10.1007/s00432-025-06183-0
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author Mingzhen Yang
Zhihui Lu
Bangzhong Liu
Guanghua Liu
Mingfang Shi
Ping Wang
author_facet Mingzhen Yang
Zhihui Lu
Bangzhong Liu
Guanghua Liu
Mingfang Shi
Ping Wang
author_sort Mingzhen Yang
collection DOAJ
description Abstract Purpose Low-intensity pulsed ultrasound (LIPUS) is an effective ancillary treatment modality for various malignancies. However, the mechanisms underlying the role of LIPUS in cancer treatment have not been fully elucidated. We investigated the effects and underlying mechanism of LIPUS on the proliferation, apoptosis, migration, and invasion of hepatocellular carcinoma (HCC) cells. Methods The HCC cell lines SMMC7721 and HCCLM3 were exposed to 1 MHz LIPUS at intensities of 0.5, 1.0, 1.5 W/cm2 for 60 s. Cell morphology, viability, apoptosis, colony formation, migration, and invasion were assessed. Intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential were evaluated using a ROS assay kit and a JC-1 staining kit. Western blotting was performed to quantify changes in matrix metallopeptidases and epithelial-mesenchymal transition-related proteins. Orthotopic Hep3B-Luc tumor-bearing mice were treated with LIPUS at 1.5 W/cm2 or 0 W/cm2 and growth trend was measured. Results The results showed that different intensities of ultrasound affected cellular activity, inhibited cell proliferation and cloning, facilitated intracellular cytoskeletal protein reorganization, and induced cell apoptosis, particularly at the intensity of 1.5 W/cm2, through the ROS/mitochondria pathway. LIPUS enhanced SMCC7721 and HCCLM3 cell migration and invasion in a dose-dependent manner by regulating matrix metallopeptidases and epithelial-mesenchymal transition-related proteins. In vivo experiments confirmed the inhibitory effect of LIPUS at 1.5 W/cm2 on tumor growth. Conclusions Although LIPUS induced cell apoptosis and inhibited cell proliferation, it also promoted the invasion and metastasis of HCC cells under certain conditions, which was related to the regulation of matrix metallopeptidases and epithelial-mesenchymal transition-related proteins.
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spelling doaj-art-78f12a0badbe4688b6f7c55d55dc26fc2025-08-20T03:10:18ZengSpringerJournal of Cancer Research and Clinical Oncology1432-13352025-04-01151411610.1007/s00432-025-06183-0Low-intensity pulsed ultrasound affects proliferation and migration of human hepatocellular carcinoma cellsMingzhen Yang0Zhihui Lu1Bangzhong Liu2Guanghua Liu3Mingfang Shi4Ping Wang5Department of Rehabilitation, Zhongshan Hospital, Fudan UniversityDepartment of Rehabilitation, Zhongshan Hospital, Fudan UniversityDepartment of Rehabilitation, Zhongshan Hospital, Fudan UniversityDepartment of Rehabilitation, Zhongshan Hospital, Fudan UniversityDepartment of Rehabilitation, Zhongshan Hospital, Fudan UniversityDepartment of Rehabilitation, Zhongshan Hospital, Fudan UniversityAbstract Purpose Low-intensity pulsed ultrasound (LIPUS) is an effective ancillary treatment modality for various malignancies. However, the mechanisms underlying the role of LIPUS in cancer treatment have not been fully elucidated. We investigated the effects and underlying mechanism of LIPUS on the proliferation, apoptosis, migration, and invasion of hepatocellular carcinoma (HCC) cells. Methods The HCC cell lines SMMC7721 and HCCLM3 were exposed to 1 MHz LIPUS at intensities of 0.5, 1.0, 1.5 W/cm2 for 60 s. Cell morphology, viability, apoptosis, colony formation, migration, and invasion were assessed. Intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential were evaluated using a ROS assay kit and a JC-1 staining kit. Western blotting was performed to quantify changes in matrix metallopeptidases and epithelial-mesenchymal transition-related proteins. Orthotopic Hep3B-Luc tumor-bearing mice were treated with LIPUS at 1.5 W/cm2 or 0 W/cm2 and growth trend was measured. Results The results showed that different intensities of ultrasound affected cellular activity, inhibited cell proliferation and cloning, facilitated intracellular cytoskeletal protein reorganization, and induced cell apoptosis, particularly at the intensity of 1.5 W/cm2, through the ROS/mitochondria pathway. LIPUS enhanced SMCC7721 and HCCLM3 cell migration and invasion in a dose-dependent manner by regulating matrix metallopeptidases and epithelial-mesenchymal transition-related proteins. In vivo experiments confirmed the inhibitory effect of LIPUS at 1.5 W/cm2 on tumor growth. Conclusions Although LIPUS induced cell apoptosis and inhibited cell proliferation, it also promoted the invasion and metastasis of HCC cells under certain conditions, which was related to the regulation of matrix metallopeptidases and epithelial-mesenchymal transition-related proteins.https://doi.org/10.1007/s00432-025-06183-0ApoptosisEpithelial-mesenchymal transitionHepatocellular carcinomaLow-intensity pulsed ultrasound
spellingShingle Mingzhen Yang
Zhihui Lu
Bangzhong Liu
Guanghua Liu
Mingfang Shi
Ping Wang
Low-intensity pulsed ultrasound affects proliferation and migration of human hepatocellular carcinoma cells
Journal of Cancer Research and Clinical Oncology
Apoptosis
Epithelial-mesenchymal transition
Hepatocellular carcinoma
Low-intensity pulsed ultrasound
title Low-intensity pulsed ultrasound affects proliferation and migration of human hepatocellular carcinoma cells
title_full Low-intensity pulsed ultrasound affects proliferation and migration of human hepatocellular carcinoma cells
title_fullStr Low-intensity pulsed ultrasound affects proliferation and migration of human hepatocellular carcinoma cells
title_full_unstemmed Low-intensity pulsed ultrasound affects proliferation and migration of human hepatocellular carcinoma cells
title_short Low-intensity pulsed ultrasound affects proliferation and migration of human hepatocellular carcinoma cells
title_sort low intensity pulsed ultrasound affects proliferation and migration of human hepatocellular carcinoma cells
topic Apoptosis
Epithelial-mesenchymal transition
Hepatocellular carcinoma
Low-intensity pulsed ultrasound
url https://doi.org/10.1007/s00432-025-06183-0
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