Targeting hepatocarcinogenesis model in C56BL6 mice with pan-aurora kinase inhibitor Danusertib

Area of Science:

• Oncology
• Molecular Biology
• Hepatology

Background:

• Hepatocellular carcinoma (HCC) is a significant global health concern.
• Aurora kinases (AURK) play a critical role in cell cycle regulation and cancer progression.
• Understanding AURK's role in hepatocarcinogenesis is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the expression of Aurora kinases (AURK) in a mouse model of liver cancer.
• To evaluate the anticancer effects of the pan-aurora kinase inhibitor Danusertib.
• To elucidate the impact of AURK inhibition on tumor development and key molecular pathways.

Main Methods:

• Diethylnitrosamine (DEN)-induced hepatocarcinogenesis model in C56Bl6 mice.
• Treatment with the pan-aurora kinase inhibitor Danusertib.
• Immunohistochemistry (IHC) for Ki-67, INCENP, cleaved caspase-3, NF-κB p65, c-Jun, and β-catenin.
• Serum level determination for C-MET/HGFR and BAD.

Main Results:

• Inhibition of AURK significantly reduced the number of DEN-induced liver tumors.
• Apoptosis and proliferation markers were low in both DEN-induced and anti-AURK groups.
• Nuclear INCENP was abundant in hepatocellular adenoma cells of DEN-treated mice but decreased markedly upon anti-AURK treatment.
• Expression of β-catenin, NF-kB, and c-Jun remained unchanged between AURK-depleted and non-depleted groups.

Conclusions:

• Depletion of AURK effectively reduced the incidence of DEN-induced hepatic tumors.
• AURK inhibition did not significantly alter the size of the developed liver tumors.
• Targeting AURK presents a potential strategy for reducing liver tumor multiplicity.