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Article

Increased efficacy of CDDP in a xenograft model of hepatoblastoma using the apoptosis sensitizer ABT-737

  • Authors:
    • Justus Lieber
    • Alexander Dewerth
    • Julia Wenz
    • Bettina Kirchner
    • Carmen Eicher
    • Steven W. Warmann
    • Jörg Fuchs
    • Sorin Armeanu-Ebinger
  • View Affiliations / Copyright

    Affiliations: Department of Paediatric Surgery and Paediatric Urology, University Children's Hospital, 72076 Tübingen, Germany
  • Pages: 646-652
    |
    Published online on: November 27, 2012
       https://doi.org/10.3892/or.2012.2150
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Abstract

The response of standard-risk hepatoblastoma (HB) to neoadjuvant cisplatin (CDDP) chemotherapy is excellent; however, in high-risk HB, drug resistance remains a major challenge. Alternative therapeutic strategies may consider combining cytotoxic drugs with apoptosis sensitizers as this has shown additive effects in various types of malignancies. Analysis of published expression databases have revealed an anti-apoptosis state in HB samples. Herein, we evaluated the synergistic effects of ABT-737 as a modulator of apoptosis in combination with CDDP in HB. To this end, clonogenic assays were performed with HepT1 and HUH6 HB cells to evaluate the synergistic effects of CDDP and ABT-737. Combination treatment with CDDP and ABT-737 reduced the clonogenicity of HB cells more than 5-fold compared to treatment with CDDP alone. Furthermore, the HUH6 mixed-type HB cells showed higher sensitivity to CDDP and combination treatment compared to the HepT1 embryonal-type cells. Subcutaneous HUH6 tumors in NOD/LtSz-scid IL2Rγnull mice were treated with CDDP (1.25 and 3 mg/kg body weight, n=6), ABT-737 (100 mg/kg, n=5) and the combination of both agents (n=5). Combined treatment led to a significantly reduced tumor growth compared to CDDP treatment alone (p<0.02). When using higher doses of CDDP (3 mg/kg) alone or in combination with ABT-737, dose-dependent toxicity was observed in this mouse strain. In conclusion, our results demonstrated the enhancement of chemotherapy efficacy by using modulators of apoptosis together with cytotoxic agents. Additive effects of ABT-737 may allow reduction in CDDP dosages with maintenance of antitumor activity. Sensitizing HB to apoptosis may also render resistant HB susceptible to established chemotherapy regimens.
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Copy and paste a formatted citation
Spandidos Publications style
Lieber J, Dewerth A, Wenz J, Kirchner B, Eicher C, Warmann SW, Fuchs J and Armeanu-Ebinger S: Increased efficacy of CDDP in a xenograft model of hepatoblastoma using the apoptosis sensitizer ABT-737. Oncol Rep 29: 646-652, 2013.
APA
Lieber, J., Dewerth, A., Wenz, J., Kirchner, B., Eicher, C., Warmann, S.W. ... Armeanu-Ebinger, S. (2013). Increased efficacy of CDDP in a xenograft model of hepatoblastoma using the apoptosis sensitizer ABT-737. Oncology Reports, 29, 646-652. https://doi.org/10.3892/or.2012.2150
MLA
Lieber, J., Dewerth, A., Wenz, J., Kirchner, B., Eicher, C., Warmann, S. W., Fuchs, J., Armeanu-Ebinger, S."Increased efficacy of CDDP in a xenograft model of hepatoblastoma using the apoptosis sensitizer ABT-737". Oncology Reports 29.2 (2013): 646-652.
Chicago
Lieber, J., Dewerth, A., Wenz, J., Kirchner, B., Eicher, C., Warmann, S. W., Fuchs, J., Armeanu-Ebinger, S."Increased efficacy of CDDP in a xenograft model of hepatoblastoma using the apoptosis sensitizer ABT-737". Oncology Reports 29, no. 2 (2013): 646-652. https://doi.org/10.3892/or.2012.2150
Copy and paste a formatted citation
x
Spandidos Publications style
Lieber J, Dewerth A, Wenz J, Kirchner B, Eicher C, Warmann SW, Fuchs J and Armeanu-Ebinger S: Increased efficacy of CDDP in a xenograft model of hepatoblastoma using the apoptosis sensitizer ABT-737. Oncol Rep 29: 646-652, 2013.
APA
Lieber, J., Dewerth, A., Wenz, J., Kirchner, B., Eicher, C., Warmann, S.W. ... Armeanu-Ebinger, S. (2013). Increased efficacy of CDDP in a xenograft model of hepatoblastoma using the apoptosis sensitizer ABT-737. Oncology Reports, 29, 646-652. https://doi.org/10.3892/or.2012.2150
MLA
Lieber, J., Dewerth, A., Wenz, J., Kirchner, B., Eicher, C., Warmann, S. W., Fuchs, J., Armeanu-Ebinger, S."Increased efficacy of CDDP in a xenograft model of hepatoblastoma using the apoptosis sensitizer ABT-737". Oncology Reports 29.2 (2013): 646-652.
Chicago
Lieber, J., Dewerth, A., Wenz, J., Kirchner, B., Eicher, C., Warmann, S. W., Fuchs, J., Armeanu-Ebinger, S."Increased efficacy of CDDP in a xenograft model of hepatoblastoma using the apoptosis sensitizer ABT-737". Oncology Reports 29, no. 2 (2013): 646-652. https://doi.org/10.3892/or.2012.2150
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