ArticleSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society2022
Perindopril sensitizes hepatocellular carcinoma to chemotherapy: A possible role of leptin / Wnt/ β-catenin axis with subsequent inhibition of liver cancer stem cells.
Article in Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Repositioning Perindopril for Mitigation of Methotrexate-Induced Hepatotoxicity in Rats.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Perindopril Ameliorates Sodium Valproate-Induced Rat Model of Autism: Involvement of Sirtuin-1, JAK2/STAT3 Axis, PI3K/Akt/GSK-3β Pathway, and PPAR-Gamma Signaling.Medicina (Kaunas, Lithuania) · 2024Article
- Clinical Significance of Plasma Leptin and Its Receptors mRNA Expression in Craniopharyngiomas: A Prospective Study.Biomolecules · 2023Article
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Authors and funding
3 authors.
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Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. The major challenge in managing HCC is the resistance to chemotherapy. Leptin hormone is associated with different oncogenic pathways implicated in drug resistance. Angiotensin II was found to decrease the production and secretion of leptin. 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. Conclusion: This study presents perindopril as a potential chemosensitizer agent that works through decreased expression of the leptin / Wnt / β-catenin pathway.
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