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Published on: March 18, 2014
5-Aminolevulinic Acid-Based Sonodynamic Therapy Induces the Apoptosis of Osteosarcoma in Mice
Yongning Li1, Qi Zhou2, Zheng Hu2
1School of Life Science and Technology, Harbin Institute of Technology, Harbin, 150080, China.
Objective:
Sonodynamic therapy (SDT) is promising for treatment of cancer, but its effect on osteosarcoma is unclear. This study examined the effect of 5-Aminolevulinic Acid (5-ALA)-based SDT on the growth of implanted osteosarcoma and their potential mechanisms in vivo and in vitro.
Methods:
The dose and metabolism of 5-ALA and ultrasound periods were optimized in a mouse model of induced osteosarcoma and in UMR-106 cells. The effects of ALA-SDT on the proliferation and apoptosis of UMR-106 cells and the growth of implanted osteosarcoma were examined. The levels of mitochondrial membrane potential (ΔψM), ROS production, BcL-2, Bax, p53 and caspase 3 expression in UMR-106 cells were determined.
Results:
Treatment with 5-ALA for eight hours was optimal for ALA-SDT in the mouse tumor model and treatment with 2 mM 5-ALA for 6 hours and ultrasound (1.0 MHz 2.0 W/cm2) for 7 min were optimal for UMR-106 cells. SDT, but not 5-ALA, alone inhibited the growth of implanted osteosarcoma in mice (P<0.01) and reduced the viability of UMR-106 cells (p<0.05). ALA-SDT further reduced the tumor volumes and viability of UMR-106 cells (p<0.01 for both). Pre-treatment with 5-ALA significantly enhanced the SDT-mediated apoptosis (p<0.01) and morphological changes. Furthermore, ALA-SDT significantly reduced the levels of ΔψM, but increased levels of ROS in UMR-106 cells (p<0.05 or p<0.01 vs. the Control or the Ultrasound). Moreover, ALA-SDT inhibited the proliferation of osteosarcoma cells and BcL-2 expression, but increased levels of Bax, p53 and caspase 3 expression in the implanted osteosarcoma tissues (p<0.05 or p<0.01 vs. the Control or the Ultrasound).
Conclusions:
The ALA-SDT significantly inhibited osteosarcoma growth in vivo and reduced UMR-106 cell survival by inducing osteosarcoma cell apoptosis through the ROS-related mitochondrial pathway.
Insights
5-Aminolevulinic Acid (5-ALA)-based sonodynamic therapy (SDT) effectively inhibits osteosarcoma growth and UMR-106 cell survival. This cancer treatment works by inducing apoptosis via a reactive oxygen species (ROS)-related mitochondrial pathway.
Area of Science:
- Oncology
- Biomedical Engineering
- Photodynamic Therapy
Background:
- Osteosarcoma remains a challenging cancer with limited treatment options.
- Sonodynamic therapy (SDT) shows promise for cancer treatment, but its efficacy against osteosarcoma requires further investigation.
Purpose of the Study:
- To evaluate the efficacy of 5-Aminolevulinic Acid (5-ALA)-based SDT against osteosarcoma.
- To elucidate the underlying mechanisms of ALA-SDT in vitro and in vivo.
Main Methods:
- Optimized 5-ALA dosage and ultrasound parameters in an osteosarcoma mouse model and UMR-106 cells.
- Assessed the impact of ALA-SDT on cell proliferation, apoptosis, mitochondrial membrane potential, and reactive oxygen species (ROS) production.
- Quantified the expression of key proteins involved in apoptosis, including Bcl-2, Bax, p53, and caspase-3.
Main Results:
- Optimized treatment involved 5-ALA for 8 hours in vivo and 2 mM 5-ALA for 6 hours with ultrasound (1.0 MHz, 2.0 W/cm²) for 7 minutes in vitro.
- ALA-SDT significantly inhibited osteosarcoma tumor growth and UMR-106 cell viability compared to SDT or 5-ALA alone.
- ALA-SDT induced apoptosis by decreasing mitochondrial membrane potential and increasing ROS production, alongside altered expression of apoptosis-related proteins.
Conclusions:
- 5-ALA-based SDT demonstrates significant anti-tumor effects against osteosarcoma.
- The therapeutic mechanism involves the induction of apoptosis through a ROS-mediated mitochondrial pathway.
- ALA-SDT presents a promising therapeutic strategy for osteosarcoma treatment.
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