Therapeutic potential of CDK-inhibitors in hepatoblastoma

Introduction: The evaluation of new drugs for the effective treatment of high-risk hepatoblastoma (HB) patients is still of utmost importance. Because deregulation of the cell cycle is a hallmark of cancer, we suggest that cyclin-dependent kinase (CDK)-inhibitors might be a therapeutic option.

Methods: Growth inhibition was assessed by MTT-assays, apoptosis by Annexin V staining and Western blot, and gene expression by real-time PCR.

Results: CDKs are frequently overexpressed in HB primary tumors. The CDK-inhibitors Olomoucine and Roscovitine show a dose-dependent cytotoxic effect on the viability of HB cells. Moreover, a massive induction of apoptosis, as evidenced by membrane asymmetry and proteolytic cleavage of caspase 3 and PARP was found. Most interestingly, CDK-inhibitors influenced kinase activity and reduce expression of components of the hedgehog signaling pathway.

Conclusion: The dramatic effects of CDK-inhibitors on growth and important signaling pathways of HB cells recommend these drugs as hopeful new agents for the treatment of HB.