Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth

  • Authors:
    • Naoya Kawabata
    • Kosei Ijiri
    • Yasuhiro Ishidou
    • Takuya Yamamoto
    • Hiroko Nagao
    • Satoshi Nagano
    • Shingo Maeda
    • Setsuro Komiya
    • Takao Setoguchi
  • View Affiliations

  • Published online on: June 14, 2011     https://doi.org/10.3892/ijo.2011.1076
  • Pages: 899-906
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Abstract

The Hedgehog pathway functions as an organizer in embryonic development. Recent studies have shown that mutation of the PTCH1 gene involved in the Hedgehog pathway affects rhabdomyosarcoma development. However, the expression of Hedgehog pathway molecules in human rhabdomyosarcoma cells has not been well clarified. In addition, the effect of pharmacological inhibition of the Hedgehog pathway is not known. We investigated the expression of the genes involved in the Hedgehog pathway using human rhabdomyosarcoma cell lines and biopsy specimens. Further, we evaluated the effect of pharmacological inhibition of the Hedgehog pathway using cyclopamine or GANT61 by WST assay, cell proliferation assay and cell death detection assay. Real-time PCR revealed that human rhabdomyosarcoma cell lines and biopsy specimens overexpressed the following genes: Sonic hedgehog, Indian hedgehog, Desert hedgehog, PTCH1, SMO, GLI1, GLI2 and ULK3. Immunohistochemistry revealed that rhabdomyosarcoma cell lines and biopsy specimens expressed SMO and GLI2. Inhibition of SMO by cyclopamine slowed the growth of human rhabdomyosarcoma cell lines. Similarly, inhibition of GLI by GANT61 slowed the growth of human rhabdomyosarcoma cell lines. Inhibition of cell proliferation and apoptotic cell death together prevented the growth of rhabdomyosarcoma cells by cyclopamine and GANT61 treatment. Our findings suggest that pharmacological inhibition of the Hedgehog pathway may be a useful approach for treating rhabdomyosarcoma patients.

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October 2011
Volume 39 Issue 4

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

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Spandidos Publications style
Kawabata N, Ijiri K, Ishidou Y, Yamamoto T, Nagao H, Nagano S, Maeda S, Komiya S and Setoguchi T: Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth. Int J Oncol 39: 899-906, 2011.
APA
Kawabata, N., Ijiri, K., Ishidou, Y., Yamamoto, T., Nagao, H., Nagano, S. ... Setoguchi, T. (2011). Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth. International Journal of Oncology, 39, 899-906. https://doi.org/10.3892/ijo.2011.1076
MLA
Kawabata, N., Ijiri, K., Ishidou, Y., Yamamoto, T., Nagao, H., Nagano, S., Maeda, S., Komiya, S., Setoguchi, T."Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth". International Journal of Oncology 39.4 (2011): 899-906.
Chicago
Kawabata, N., Ijiri, K., Ishidou, Y., Yamamoto, T., Nagao, H., Nagano, S., Maeda, S., Komiya, S., Setoguchi, T."Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth". International Journal of Oncology 39, no. 4 (2011): 899-906. https://doi.org/10.3892/ijo.2011.1076