Carbon-Ion Beam Irradiation Alone or in Combination with Zoledronic acid Effectively Kills Osteosarcoma Cells.
Eun Ho KimMi-Sook KimAkihisa TakahashiMasao SuzukiGuillaume VaresAkiko UzawaAkira FujimoriTatsuya OhnoSei SaiPublished in: Cancers (2020)
Osteosarcoma (OSA) is the most common malignant bone tumor in children and adolescents. The overall five-year survival rate for all bone cancers is below 70%; however, when the cancer has spread beyond the bone, it is about 15-30%. Herein, we evaluated the effects of carbon-ion beam irradiation alone or in combination with zoledronic acid (ZOL) on OSA cells. Carbon-ion beam irradiation in combination with ZOL significantly inhibited OSA cell proliferation by arresting cell cycle progression and initiating KHOS and U2OS cell apoptosis, compared to treatments with carbon-ion beam irradiation, X-ray irradiation, and ZOL alone. Moreover, we observed that this combination greatly inhibited OSA cell motility and invasion, accompanied by the suppression of the Pi3K/Akt and MAPK signaling pathways, which are related to cell proliferation and survival, compared to individual treatments with carbon-ion beam or X-ray irradiation, or ZOL. Furthermore, ZOL treatment upregulated microRNA (miR)-29b expression; the combination with a miR-29b mimic further decreased OSA cell viability via activation of the caspase 3 pathway. Thus, ZOL-mediated enhancement of carbon-ion beam radiosensitivity may occur via miR-29b upregulation; co-treatment with the miR-29b mimic further decreased OSA cell survival. These findings suggest that the carbon-ion beam irradiation in combination with ZOL has high potential to increase OSA cell death.
Keyphrases
- cell proliferation
- obstructive sleep apnea
- cell cycle
- cell death
- induced apoptosis
- positive airway pressure
- electron microscopy
- signaling pathway
- cell cycle arrest
- pi k akt
- high resolution
- poor prognosis
- bone mineral density
- monte carlo
- computed tomography
- magnetic resonance imaging
- stem cells
- oxidative stress
- magnetic resonance
- sleep apnea
- mass spectrometry
- epithelial mesenchymal transition
- mesenchymal stem cells
- postmenopausal women
- combination therapy
- pseudomonas aeruginosa
- papillary thyroid
- cell therapy
- bone regeneration
- lymph node metastasis
- free survival
- squamous cell
- cell migration