Zoledronic acid significantly enhances radiation‑induced apoptosis against human fibrosarcoma cells by inhibiting radioadaptive signaling

  • Authors:
    • Kazutaka Koto
    • Hiroaki Murata
    • Shinya Kimura
    • Yasushi Sawai
    • Naoyuki Horie
    • Takaaki Matsui
    • Kazuteru Ryu
    • Eishi Ashihara
    • Taira Maekawa
    • Toshikazu Kubo
    • Shinji Fushiki
  • View Affiliations

  • Published online on: December 12, 2012     https://doi.org/10.3892/ijo.2012.1735
  • Pages: 525-534
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Abstract

Zoledronic acid (ZOL), a third-generation bisphosphonate, inhibits bone resorption, as well as exhibiting direct antitumor activity. To date, however, the combined effects of ZOL and ionizing radiation (IR) have not been assessed in patients with soft tissue sarcoma. We have, therefore, assessed the combined effects of ZOL and IR in fibrosarcoma cells. HT1080 fibrosarcoma cells were treated with ZOL and/or IR, together or sequentially and the antitumor effects were assessed. We found that ZOL significantly enhanced IR-induced apoptosis, especially when cells were treated with ZOL followed by IR. We, therefore, assessed the detailed mechanism of sequential treatment with ZOL and IR. Cells in G2 and M phases, the most radiosensitive phases of the cell cycle, were not increased by low concentrations of ZOL. However, the levels of expression of Akt, ERK1/2 and NF-κB proteins, all of which are related to radioadaptive resistance, were increased within a short time after irradiation with 3 Gy, and this expression was inhibited by a low concentration of ZOL, which blocked the prenylation of small GTPases. This sequential treatment also increased the generation of reactive oxygen species (ROS). These results suggest that the combination of ZOL with IR may be beneficial in treating patients with soft tissue sarcoma.
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February 2013
Volume 42 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Koto, K., Murata, H., Kimura, S., Sawai, Y., Horie, N., Matsui, T. ... Fushiki, S. (2013). Zoledronic acid significantly enhances radiation‑induced apoptosis against human fibrosarcoma cells by inhibiting radioadaptive signaling. International Journal of Oncology, 42, 525-534. https://doi.org/10.3892/ijo.2012.1735
MLA
Koto, K., Murata, H., Kimura, S., Sawai, Y., Horie, N., Matsui, T., Ryu, K., Ashihara, E., Maekawa, T., Kubo, T., Fushiki, S."Zoledronic acid significantly enhances radiation‑induced apoptosis against human fibrosarcoma cells by inhibiting radioadaptive signaling". International Journal of Oncology 42.2 (2013): 525-534.
Chicago
Koto, K., Murata, H., Kimura, S., Sawai, Y., Horie, N., Matsui, T., Ryu, K., Ashihara, E., Maekawa, T., Kubo, T., Fushiki, S."Zoledronic acid significantly enhances radiation‑induced apoptosis against human fibrosarcoma cells by inhibiting radioadaptive signaling". International Journal of Oncology 42, no. 2 (2013): 525-534. https://doi.org/10.3892/ijo.2012.1735