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

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.