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Effect of low- and high-linear energy transfer radiation on in vitro and orthotopic in vivo models of osteosarcoma by activation of caspase-3 and -9

  • Authors:
    • Eun Ho Kim
    • Mi-Sook Kim
    • Kyung-Hee Lee
    • Sei Sai
    • Youn Kyoung Jeong
    • Jae-Soo Koh
    • Chang-Bae Kong
  • View Affiliations / Copyright

    Affiliations: Division of Heavy Ion Clinical Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea, Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea, Department of Orthopaedic Surgery, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea, Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, Chiba, Japan, Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea, Department of Pathology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea
    Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1124-1134
    |
    Published online on: August 25, 2017
       https://doi.org/10.3892/ijo.2017.4102
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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.
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Copy and paste a formatted citation
Spandidos Publications style
Kim EH, Kim M, Lee K, Sai S, Jeong YK, Koh J and Kong C: Effect of low- and high-linear energy transfer radiation on in vitro and orthotopic in vivo models of osteosarcoma by activation of caspase-3 and -9. Int J Oncol 51: 1124-1134, 2017.
APA
Kim, E.H., Kim, M., Lee, K., Sai, S., Jeong, Y.K., Koh, J., & Kong, C. (2017). Effect of low- and high-linear energy transfer radiation on in vitro and orthotopic in vivo models of osteosarcoma by activation of caspase-3 and -9. International Journal of Oncology, 51, 1124-1134. https://doi.org/10.3892/ijo.2017.4102
MLA
Kim, E. H., Kim, M., Lee, K., Sai, S., Jeong, Y. K., Koh, J., Kong, C."Effect of low- and high-linear energy transfer radiation on in vitro and orthotopic in vivo models of osteosarcoma by activation of caspase-3 and -9". International Journal of Oncology 51.4 (2017): 1124-1134.
Chicago
Kim, E. H., Kim, M., Lee, K., Sai, S., Jeong, Y. K., Koh, J., Kong, C."Effect of low- and high-linear energy transfer radiation on in vitro and orthotopic in vivo models of osteosarcoma by activation of caspase-3 and -9". International Journal of Oncology 51, no. 4 (2017): 1124-1134. https://doi.org/10.3892/ijo.2017.4102
Copy and paste a formatted citation
x
Spandidos Publications style
Kim EH, Kim M, Lee K, Sai S, Jeong YK, Koh J and Kong C: Effect of low- and high-linear energy transfer radiation on in vitro and orthotopic in vivo models of osteosarcoma by activation of caspase-3 and -9. Int J Oncol 51: 1124-1134, 2017.
APA
Kim, E.H., Kim, M., Lee, K., Sai, S., Jeong, Y.K., Koh, J., & Kong, C. (2017). Effect of low- and high-linear energy transfer radiation on in vitro and orthotopic in vivo models of osteosarcoma by activation of caspase-3 and -9. International Journal of Oncology, 51, 1124-1134. https://doi.org/10.3892/ijo.2017.4102
MLA
Kim, E. H., Kim, M., Lee, K., Sai, S., Jeong, Y. K., Koh, J., Kong, C."Effect of low- and high-linear energy transfer radiation on in vitro and orthotopic in vivo models of osteosarcoma by activation of caspase-3 and -9". International Journal of Oncology 51.4 (2017): 1124-1134.
Chicago
Kim, E. H., Kim, M., Lee, K., Sai, S., Jeong, Y. K., Koh, J., Kong, C."Effect of low- and high-linear energy transfer radiation on in vitro and orthotopic in vivo models of osteosarcoma by activation of caspase-3 and -9". International Journal of Oncology 51, no. 4 (2017): 1124-1134. https://doi.org/10.3892/ijo.2017.4102
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