Yang Mingzhen, Lu Zhihui, Liu Bangzhong, Liu Guanghua, Shi Mingfang, Wang Ping
Department of Rehabilitation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Shanghai Institute of Rehabilitation with Integrated Western and Chinese Traditional Medicine, Shanghai, 200032, China.
J Cancer Res Clin Oncol. 2025 Apr 10;151(4):136. doi: 10.1007/s00432-025-06183-0.
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.
The HCC cell lines SMMC7721 and HCCLM3 were exposed to 1 MHz LIPUS at intensities of 0.5, 1.0, 1.5 W/cm 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/cm or 0 W/cm and growth trend was measured.
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/cm, 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/cm on tumor growth.
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.
低强度脉冲超声（LIPUS）是治疗多种恶性肿瘤的一种有效辅助治疗方式。然而，LIPUS在癌症治疗中发挥作用的潜在机制尚未完全阐明。我们研究了LIPUS对肝癌（HCC）细胞增殖、凋亡、迁移和侵袭的影响及其潜在机制。
将肝癌细胞系SMMC7721和HCCLM3暴露于频率为1MHz、强度分别为0.5、1.0、1.5W/cm²的LIPUS下60秒。评估细胞形态、活力、凋亡、集落形成、迁移和侵袭情况。使用活性氧（ROS）检测试剂盒和JC-1染色试剂盒评估细胞内ROS水平和线粒体膜电位。采用蛋白质免疫印迹法量化基质金属肽酶和上皮-间质转化相关蛋白的变化。对原位接种Hep3B-Luc的荷瘤小鼠分别给予1.5W/cm²或0W/cm²的LIPUS治疗，并测量肿瘤生长趋势。
结果显示，不同强度的超声会影响细胞活性，抑制细胞增殖和克隆，促进细胞内细胞骨架蛋白重组，并诱导细胞凋亡，尤其是在强度为1.5W/cm²时，通过ROS/线粒体途径发挥作用。LIPUS通过调节基质金属肽酶和上皮-间质转化相关蛋白，以剂量依赖的方式增强了SMMC7721和HCCLM3细胞的迁移和侵袭能力。体内实验证实了1.5W/cm²的LIPUS对肿瘤生长具有抑制作用。
尽管LIPUS诱导细胞凋亡并抑制细胞增殖，但在某些条件下它也会促进肝癌细胞的侵袭和转移，这与基质金属肽酶和上皮-间质转化相关蛋白的调节有关。
