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Abstract​​

Osteosarcoma (OS) is a malignant tumor of the bone derived from primitive transformed cells of the mesenchymal origin. Local low-linear energy transfer (LET) radiotherapy has limited benefits on OS owing to its radioresistance. Thus, this study aimed to investigate the effects of high-LET radiation on human OS. Therefore, the human OS cell lines, U2O2 and KHOS/NP, were examined in vitro, or an orthotopic mouse xenograft model was studied in vivo after treatment with low-LET (gamma-ray) and high-LET (neutron) radiation. Notably, OS cells were significantly more sensitive to high-LET radiation in vitro and in the orthotopic xenograft tumor model. Specifically, neutron radiation treatment increased the relative percentage of apoptotic sub-G1 phase cells via caspase-3/9 activation; increased intracellular reactive oxygen species, autophagy, and DNA damage; and decreased invasion and migration. Similarly, the mean size of gamma-irradiated (8 Gy) orthotopic KHOS/NP OS was 195 mm3 at 6 weeks after gamma-irradiation (8 Gy), but it was only 150 mm3 in mice treated with high-LET neutron radiotherapy. Significantly, our results provide a rationale for the use of high-LET radiotherapy to treat patients with OS.

Author information

Kim EH1, Kim MS2, Lee KH3, Sai S4, Jeong YK5, Koh JS6, Kong CB3.

1 Division of Heavy Ion Clinical Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea.

2 Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea.

3 Department of Orthopaedic Surgery, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea.

4 Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, Chiba, Japan.

5 Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea.

6 Department of Pathology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea.