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Pharmacological inhibition of beta-catenin in hepatoblastoma cells

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Abstract

Purpose

The proto-oncogene beta-catenin is linked to an abnormal activation of the Wnt/beta-catenin-pathway and shows mutations in 50–90 % of hepatoblastoma (HB). Corresponding, the recently published murine orthotopic HB model differs from the former subcutaneous model by nuclear beta-catenin distribution. As the nuclear localization of beta-catenin is considered to reflect a more aggressive tumor growth, the influence of beta-catenin inhibition on cell viability and drug-efficiency in HB cells was analyzed.

Methods

Beta-catenin distribution in HB cells was analyzed by immunofluorescence. The influence of beta-catenin inhibitors Celecoxib, Etodolac, ICG001, and MET kinase inhibitor (SU11274) alone and in combination with cisplatin (CDDP) on HB cell lines (HuH6, HepT1) was evaluated by cell viability assays and BrdU incorporation.

Results

Celecoxib and ICG001 reduced dose-dependently HB cell viability and decreased nuclear beta-catenin in cultivated HB cells. Etodolac was without influence at concentrations up to 100 μM. Combinations of Celecoxib or ICG001 with MET kinase inhibitor or CDDP resulted in additive reduction of cell viability.

Conclusion

Pharmaceutical beta-catenin inhibitors can modulate the nuclear localization of beta-catenin and reduce cell viability of HB cells in vitro. These promising effects might optimize the outcome of high-risk HB. The orthotopic HB model is a suitable basis for further in vivo studies.

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Authors and Affiliations

  1. Department of Pediatric Surgery and Pediatric Urology, Children’s University Hospital Tuebingen, Hoppe-Seyler-Str. 3, 72076, Tuebingen, Germany

    V. Ellerkamp, J. Lieber, C. Nagel, J. Wenz, S. W. Warmann, J. Fuchs & S. Armeanu-Ebinger

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  1. V. Ellerkamp
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  2. J. Lieber
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  3. C. Nagel
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  4. J. Wenz
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  7. S. Armeanu-Ebinger
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Correspondence to V. Ellerkamp.

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Ellerkamp, V., Lieber, J., Nagel, C. et al. Pharmacological inhibition of beta-catenin in hepatoblastoma cells. Pediatr Surg Int 29, 141–149 (2013). https://doi.org/10.1007/s00383-012-3237-9

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