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Article

Targeting hedgehog signalling by arsenic trioxide reduces cell growth and induces apoptosis in rhabdomyosarcoma

  • Authors:
    • Karen A. Boehme
    • Julian J. Zaborski
    • Rosa Riester
    • Sabrina K. Schweiss
    • Ulrike Hopp
    • Frank Traub
    • Torsten Kluba
    • Rupert Handgretinger
    • Sabine B. Schleicher
  • View Affiliations / Copyright

    Affiliations: Laboratory of Cell Biology, Department of Orthopaedic Surgery, Eberhard Karls University Tuebingen, Tuebingen, Germany, Department of Orthopaedic Surgery, Eberhard Karls University, Tuebingen, Germany, Department of Haematology and Oncology, Children's Hospital, Eberhard Karls University Tuebingen, Tuebingen, Germany
  • Pages: 801-812
    |
    Published online on: December 15, 2015
       https://doi.org/10.3892/ijo.2015.3293
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Abstract

Rhabdomyosarcomas (RMS) are soft tissue tumours treated with a combination of surgery and chemotherapy. However, mortality rates remain high in case of recurrences and metastatic disease due to drug resistance and failure to undergo apoptosis. Therefore, innovative approaches targeting specific signalling pathways are urgently needed. We analysed the impact of different hedgehog (Hh) pathway inhibitors on growth and survival of six RMS cell lines using MTS assay, colony formation assay, 3D spheroid cultures, flow cytometry and western blotting. Especially the glioma-associated oncogene family (GLI) inhibitor arsenic trioxide (ATO) effectively reduced viability as well as clonal growth and induced cell death in RMS cell lines of embryonal, alveolar and sclerosing, spindle cell subtype, whereas normal skeletal muscle cells were hardly compromised by ATO. Combination of ATO with itraconazole potentiated the reduction of colony formation and spheroid size. These results show that ATO is a promising substance for treatment of relapsed and refractory RMS by directly targeting GLI transcription factors. The combination with itraconazole or other chemotherapeutic drugs has the opportunity to enforce the treatment efficiency of resistant and recurrent RMS.
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Copy and paste a formatted citation
Spandidos Publications style
Boehme KA, Zaborski JJ, Riester R, Schweiss SK, Hopp U, Traub F, Kluba T, Handgretinger R and Schleicher SB: Targeting hedgehog signalling by arsenic trioxide reduces cell growth and induces apoptosis in rhabdomyosarcoma. Int J Oncol 48: 801-812, 2016.
APA
Boehme, K.A., Zaborski, J.J., Riester, R., Schweiss, S.K., Hopp, U., Traub, F. ... Schleicher, S.B. (2016). Targeting hedgehog signalling by arsenic trioxide reduces cell growth and induces apoptosis in rhabdomyosarcoma. International Journal of Oncology, 48, 801-812. https://doi.org/10.3892/ijo.2015.3293
MLA
Boehme, K. A., Zaborski, J. J., Riester, R., Schweiss, S. K., Hopp, U., Traub, F., Kluba, T., Handgretinger, R., Schleicher, S. B."Targeting hedgehog signalling by arsenic trioxide reduces cell growth and induces apoptosis in rhabdomyosarcoma". International Journal of Oncology 48.2 (2016): 801-812.
Chicago
Boehme, K. A., Zaborski, J. J., Riester, R., Schweiss, S. K., Hopp, U., Traub, F., Kluba, T., Handgretinger, R., Schleicher, S. B."Targeting hedgehog signalling by arsenic trioxide reduces cell growth and induces apoptosis in rhabdomyosarcoma". International Journal of Oncology 48, no. 2 (2016): 801-812. https://doi.org/10.3892/ijo.2015.3293
Copy and paste a formatted citation
x
Spandidos Publications style
Boehme KA, Zaborski JJ, Riester R, Schweiss SK, Hopp U, Traub F, Kluba T, Handgretinger R and Schleicher SB: Targeting hedgehog signalling by arsenic trioxide reduces cell growth and induces apoptosis in rhabdomyosarcoma. Int J Oncol 48: 801-812, 2016.
APA
Boehme, K.A., Zaborski, J.J., Riester, R., Schweiss, S.K., Hopp, U., Traub, F. ... Schleicher, S.B. (2016). Targeting hedgehog signalling by arsenic trioxide reduces cell growth and induces apoptosis in rhabdomyosarcoma. International Journal of Oncology, 48, 801-812. https://doi.org/10.3892/ijo.2015.3293
MLA
Boehme, K. A., Zaborski, J. J., Riester, R., Schweiss, S. K., Hopp, U., Traub, F., Kluba, T., Handgretinger, R., Schleicher, S. B."Targeting hedgehog signalling by arsenic trioxide reduces cell growth and induces apoptosis in rhabdomyosarcoma". International Journal of Oncology 48.2 (2016): 801-812.
Chicago
Boehme, K. A., Zaborski, J. J., Riester, R., Schweiss, S. K., Hopp, U., Traub, F., Kluba, T., Handgretinger, R., Schleicher, S. B."Targeting hedgehog signalling by arsenic trioxide reduces cell growth and induces apoptosis in rhabdomyosarcoma". International Journal of Oncology 48, no. 2 (2016): 801-812. https://doi.org/10.3892/ijo.2015.3293
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