Effects of low-intensity pulsed ultrasound on osteosarcoma and cancer cells

Abstract

Abstract. Metastatic bone tumors cause pain and pathological fractures due to bone destruction. If we could enhance new osteogenic activities and prevent progression of osteolytic change by malignant cells, patients could achieve satisfactory activity of daily living. Low-intensity pulsed ultrasound (LIPUS), which leads to bone formation by osteoblasts, has been used for the treatment of fractures. LIPUS has been reported to enhance the effect of an anticancer drug on lymphoma and liver cancer cells. However, there have been no reports of proliferation, vascularization and migration effects on cancer cells. In this study, we investigated the effects of LIPUS treatment on cancer and osteosarcoma cells and specifically whether it promotes bone formation without accelerating proliferation of tumor cells. We used MC3T3-E1 cells, a mouse osteoblast cell line, LM8, a mouse osteosarcoma cell line, SaOS2, a human osteosarcoma cell line, 786-O, a human renal cancer cell line, PC-3, a human prostate cancer cell line, and A549, a human lung cancer cell line. The expression of extracellular signal-regulated kinase (ERK1/2), Akt, β-catenin, vascular endothelial growth factor (VEGF), and cell migration were analyzed. LIPUS stimulation did not affect proliferation of all the cells examined. The phosphorylation of ERK1/2 and Akt was induced by LIPUS stimulation in MC3T3-E1, LM8, SaOS2 and A549 cells, but not in PC-3 and 786-O cells. LIPUS stimulation did not significantly increase β-catenin. VEGF protein levels and cell migration were significantly increased only in MC3T3-E1 cells. It may be concluded that LIPUS stimulation on metastatic bone tumors induces differentiation of osteoblasts without proliferation of tumor cells. Our study suggests that LIPUS may be a new method of treatment without surgery for metastatic bone tumors.

Low‐intensity pulsed ultrasound affects growth, differentiation, migration, and epithelial‐to‐mesenchymal transition of colorectal cancer cells

“…The proliferation rate and the clonogenicity of colorectal cancer cells were not affected by LIPUS at 24 hr after the exposure (Figure 1). These results might appear apparently in contrast with the ones by Sawai et al (2012) who reported that LIPUS decreases the proliferation of osteosarcoma cells. We believe this discrepancy might be due to the different cell types used in these studies and, especially, to the different schedule of LIPUS treatment.…”

“…We believe this discrepancy might be due to the different cell types used in these studies and, especially, to the different schedule of LIPUS treatment. Indeed, the cited authors administered LIPUS for 20 min every day for the duration of their experiment (up to 72 hr) while we only administered a 30 s pulse and analyzed cells after 24 hr (Sawai et al, 2012). Experiments are ongoing to evaluate the effects of a more prolonged (chronic) exposure of cells to LIPUS.…”

Low-intensity pulsed ultrasound promotes cell motility through vinculin-controlled Rac1 GTPase activity

“…S1C) (Sawai et al, 2012). Our finding that LIPUS stimulation enhances the Rac1-dependent migration of fibroblasts (Fig.…”

Inhibitory effects of low-intensity pulsed ultrasound sonication on the proliferation of osteosarcoma cells

“…Previous reports have revealed that LIPUS stimulated the phosphorylation of ERK1/2 and Akt in osteosarcoma cell lines (21) as well as the activation of ERK1/2 in osteosarcoma cells, which have been induced to undergo apoptosis and autophagy (24). In addition, Akt may induce apoptosis via inhibition of Chk1 (25).…”

“…There have been several studies reporting that LIPUS has antitumor effects via the induction of apoptosis in cancer cells (19)(20)(21)(22)(23). For example, LIPUS was previously demonstrated to induce apoptosis by causing membrane damage in human leukemia cells (19), affecting the Ca 2+ /mitochondrial pathway in human hepatocellular carcinoma cells (23) and enhancing adjuvant chemotherapy in cases of lymphoma (20).…”