Conclusion
This study presents perindopril as a potential chemosensitizer agent that works through decreased expression of the leptin / Wnt / β-catenin pathway.
Objective
This study investigated the potential role of an ACEI perindopril as a chemosensitizer agent to sorafenib. Method: HCC was induced in mice using a single dose of diethylnitrosamine DENA (200 mg/kg) followed by phenobarbital 0.05% in drinking water for 16 weeks. Mice were then treated with perindopril (1 mg/kg/day), Sorafenib (30 mg/kg/day), or both of them for another four weeks. Leptin, VEGF, MMP-9, Cyclin D1, EpCAM, and β-catenin were measured using immunoassay while Wnt and ALDH1 were assayed using western blotting assay.
Results
Perindopril whether alone or in combination with sorafenib decrease liver enzymes and preserve the liver architecture. Our study revealed that perindopril significantly increased the antineoplastic, antiangiogenic as well as anti-metastatic effects of sorafenib. This effect was correlated with the downregulation of the leptin / Wnt / β-catenin pathway and overexpression of ALDH1 while downregulation of EpCAM.