Low intensity-pulsed ultrasound induced apoptosis of human hepatocellular carcinoma cells in vitro

• Published in: Ultrasonics Vol. 64; pp. 43 - 53
• Main Authors: Shi, Mingfang, Liu, Bangzhong, Liu, Guanghua, Wang, Ping, Yang, Mingzhen, Li, Yun, Zhou, Jian
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2016
• Subjects: Apoptosis; Apoptosis - physiology; Apoptosis - radiation effects; bcl-2-Associated X Protein - metabolism; Calcium ion; Carcinoma, Hepatocellular - pathology; Caspase 3 - metabolism; Cell Line, Tumor; Cell Proliferation; Cell Survival; DNA Fragmentation; Humans; In Vitro Techniques; Liver Neoplasms - pathology; Low intensity-pulsed ultrasound; Mitochondrial pathway; Neoplasm Proteins - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; SMMC-7721 cells; Ultrasonic Waves; Low intensity-pulsed ultrasound; Calcium ion; Mitochondrial pathway; SMMC-7721 cells; Apoptosis
• ISSN: 0041-624X; 1874-9968
• DOI: 10.1016/j.ultras.2015.07.011

•LIPUS inhibit SMMC-7721 cell viability and induce apoptosis.•The effects caused by LIPUS were dose-dependent.•Ca2+/mitochondrial pathways are the key mode of apoptosis induced by LIPUS. The present study was conducted to determine whether low intensity-pulsed ultrasound (LIPUS) could induce apoptosis of human hepatocellular carcinoma cells, SMMC-7721, and to define the mechanism of ultrasound-induced apoptosis, in vitro. MTT assay was used to measure cell proliferation. Apoptosis was investigated by multiple methods such as flow cytometry, DNA fragmentation, Ca2+ mobilizations, pro- and anti-apoptotic protein expression, and light as well as ultramicroscopic morphology. The results provide evidence that LIPUS induced a dose-dependent effect on cell viability and apoptosis of SMMC-7721 cells. Specifically, exposure of cells to >0.5W/cm2 intensity significantly increased cell apoptosis, caused shifts in cell cycle phase, and induced structural changes. Ultrasound significantly increased intracellular Ca2+ concentrations and modulated expression of caspase-3, Bcl-2 and Bax. The findings suggest that this novel technology can be used to induce SMMC-7721 apoptosis via the Ca2+/mitochondrial pathway and could potentially be of clinical use for the treatment of hepatocellular carcinoma (SMMC-7721 cell line) and other cancers.