Zoledronic acid inhibits proliferation of human fibrosarcoma cells with induction of apoptosis, and shows combined effects with other anticancer agents

  • Authors:
    • Kazutaka Koto
    • Hiroaki Murata
    • Shinya Kimura
    • Naoyuki Horie
    • Takaaki Matsui
    • Yasunori Nishigaki
    • Kazuteru Ryu
    • Tomoya Sakabe
    • Megumi Itoi
    • Eishi Ashihara
    • Taira Maekawa
    • Shinji Fushiki
    • Toshikazu Kubo
  • View Affiliations

  • Published online on: July 1, 2010     https://doi.org/10.3892/or_00000851
  • Pages: 233-239
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Third-generation bisphosphonates are known to inhibit bone resorption and also appear to exhibit direct anti-tumour activity. We previously reported that third-generation bisphosphonates such as zoledronic acid (ZOL) have a direct antitumour effect, and synergistically augment the effects of antitumor agents in osteosarcoma cells. There has been no report on the antitumor effect of ZOL against soft tissue sarcoma. The aim of this study was to evaluate the antitumor effect of this drug on a human fibrosarcoma cell line, in terms of proliferation and apoptosis, and, moreover, to evaluate the combined effects of ZOL with other antitumor drugs against the human fibrosarcoma cell line. HT1080 cells were treated with ZOL at various concentrations up to 10 µM, and then cell proliferation, cell cycle, nuclear morphology, and Western blot analyses were performed to study the antitumor effects of ZOL alone, and, moreover, HT1080 cells were treated with ZOL and other anticancer drugs such as paclitaxel, docetaxel, doxorubicin, etoposide, 5-fluorouracil, gemcitabine, cisplatin, or methotrexate to investigate the combined effects using proliferation and cell cycle analyses. We found that ZOL strongly inhibited in vitro proliferation, arrested the cell cycle between S and G2/M phases, and induced the apoptosis of human fibrosarcoma cells. Moreover, ZOL augmented the effect of antitumor agents when administered concurrently with paclitaxel, docetaxel, doxorubicin, etoposide, 5-fluorouracil, gemcitabine, and cisplatin in human fibrosarcoma cells. The treatment of fibrosarcoma with ordinary antitumor drugs is not fully effective. These findings suggest that ZOL directly affects the proliferation and survival of fibrosarcoma cells, and that the combined administration of ZOL with other antitumor agents may improve the efficacy of fibrosarcoma treatment. These results support the possibility that their combined use could be beneficial in the treatment of patients not only with various types of cancer or osteosarcoma, but also with soft tissue sarcoma.

Related Articles

Journal Cover

July 2010
Volume 24 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Koto K, Murata H, Kimura S, Horie N, Matsui T, Nishigaki Y, Ryu K, Sakabe T, Itoi M, Ashihara E, Ashihara E, et al: Zoledronic acid inhibits proliferation of human fibrosarcoma cells with induction of apoptosis, and shows combined effects with other anticancer agents. Oncol Rep 24: 233-239, 2010
APA
Koto, K., Murata, H., Kimura, S., Horie, N., Matsui, T., Nishigaki, Y. ... Kubo, T. (2010). Zoledronic acid inhibits proliferation of human fibrosarcoma cells with induction of apoptosis, and shows combined effects with other anticancer agents. Oncology Reports, 24, 233-239. https://doi.org/10.3892/or_00000851
MLA
Koto, K., Murata, H., Kimura, S., Horie, N., Matsui, T., Nishigaki, Y., Ryu, K., Sakabe, T., Itoi, M., Ashihara, E., Maekawa, T., Fushiki, S., Kubo, T."Zoledronic acid inhibits proliferation of human fibrosarcoma cells with induction of apoptosis, and shows combined effects with other anticancer agents". Oncology Reports 24.1 (2010): 233-239.
Chicago
Koto, K., Murata, H., Kimura, S., Horie, N., Matsui, T., Nishigaki, Y., Ryu, K., Sakabe, T., Itoi, M., Ashihara, E., Maekawa, T., Fushiki, S., Kubo, T."Zoledronic acid inhibits proliferation of human fibrosarcoma cells with induction of apoptosis, and shows combined effects with other anticancer agents". Oncology Reports 24, no. 1 (2010): 233-239. https://doi.org/10.3892/or_00000851