Sildenafil potentiates the cytostatic effect of doxorubicin in pediatric epithelial liver tumors

Introduction: The hepatoblastoma (HB) and pediatric hepatocellular carcinoma (pHCC) are the most common liver tumors in infancy and childhood. Treatment results have been improved particularly for the HB over the last two decades by establishing treatment regimes that combine neoadjuvant and adjuvant chemotherapy with surgery. However survival in advanced diseases is still poor. Therapeutic results for children with HCC are generally poor despite a general increase in survival rates for most solid tumours among this age group. In the present study, we want to investigate whether established phosphodiesterase 5 (PDE5) inhibitor sildenafil interacts with doxorubicin to potentiate the antitumor efficacy in pediatric epithelial liver tumors.

Methods: The growth inhibition under treatment of sildenafil in combination with doxorubicin was measured by MTT-assays, apoptosis and ROS production by flow cytometry and the intracellular signaling by Western blot.

Results: Co-treatment with sildenafil and doxorubicin resulted in a suppressed tumor cell growth and enhanced apoptosis in HepT1 and HC-AFW-1 cells, which was mediated by increased generation of reactive oxygen species.

Conclusion: In summary, these results provide evidence that sildenafil may help to optimize and complete existing therapy in pediatric epithelial liver tumors.

Erratum note:

This is a corrected version.

The publisher regrets an error in the author name “Stagno MJ” in the above article published online May 2, 2016. The author's last name was wrong and was incorrectly published as “Stango MJ”. The correct author listing appears above.