Mechanism of rat osteosarcoma cell apoptosis induced by a combination of low-intensity ultrasound and 5-aminolevulinic acid in vitro.
We investigated the killing effect of low-intensity ultrasound combined with 5-aminolevulinic acid (5-ALA) on the rat osteosarcoma cell line UMR-106. Logarithmic-phase UMR-106 cells were divided into a control group, ultrasound group and 5-ALA group. The cell apoptotic rate, production of reactive oxygen species, and the change in mitochondrial membrane potential were analyzed by flow cytometry; ultrastructural changes were observed by transmission electron microscopy. Using low-intensity ultrasound at 1.0 MHz and 2.0 W/cm(2) plus 5-ALA at a concentration of 2 mM, the apoptotic rate of the sonodynamic therapy group was 27.2 ± 3.4% which was significantly higher than that of the control group, ultrasound group, and 5-ALA group (P < 0.05). The production of reactive oxygen species was 32.6 ± 2.2% and the decrease in mitochondrial membrane potential was 39.5 ± 2.5%. The 33342 staining showed nuclear condensation and fragmentation in the ultrasound group and 5-ALA group. Structural changes in the cell membrane, mitochondria, Golgi apparatus, and other organelles observed by transmission electron microscopy included formation of apoptotic bodies. The killing effect of low-intensity ultrasound combined with 5-ALA on UMR-106 cells was significant. Cell apoptosis played a vital role in the killing effect, and the mitochondria pathway contributed to the apoptosis of UMR-106 cells.
School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
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Li
Laboratory of Photo-and Sono-Theranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin, China.
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Zhou
Laboratory of Photo-and Sono-Theranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin, China.
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Yang
Laboratory of Photo-and Sono-Theranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin, China.
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Hu
Laboratory of Photo-and Sono-Theranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin, China.
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Wang
Cardiovascular Institute, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
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Li
School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
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Cao
D000622:Aminolevulinic Acid / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D012516:Osteosarcoma / Q000378:metabolism / Q000628:therapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D014464:Ultrasonic Therapy; D000069453:Ultrasonic Waves / Q000009:adverse effects*
D017382:Reactive Oxygen Species; D000622:Aminolevulinic Acid