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- Title
Anticancer effect of propranolol on diethylnitrosamine‐induced hepatocellular carcinoma rat model.
- Authors
Tamim, Yomna M.; Nagy, Ahmed A.; Abdellah, Ahmed M.; Osman, Ahmed H.; Ismail, Amel F. M.
- Abstract
Background: Hepatocellular carcinoma (HCC) is the most widespread type of primary liver cancer. Diethylnitrosamine (DEN), a hepatotoxic hepatocarcinogenic compound, is used to induce HCC in animal models. The non‐selective β‐blocker propranolol demonstrated antiproliferative activity in many cancer types. Objective: This investigation aimed to evaluate the anticancer effect of propranolol against DEN‐induced HCC in rats. Methods: Thirty adult male rats were divided into the following groups: Group I (C, control), Group II (HCC); received DEN, 70 mg/kg body weight (b.wt.) once a week for 10 weeks, to induce HCC, and Group III (HCC/Prop); received DEN for 10 weeks for HCC induction, then received 20 mg/kg b.wt. propranolol, intraperitoneally for four successive weeks. Results: HCC was developed in rats' livers and confirmed via significant liver architecture changes, significantly elevated activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), α‐fetoprotein (AFP), total‐ and direct‐bilirubin (Bil), and a decline in albumin (ALB) level in serum. HCC group demonstrated elevated levels of malondialdehyde (MDA), nitric oxide (NO), HIF‐1α, IL‐8, NF‐κB, PGE2, TGF‐β1, VEGF, and CD8, but significant decline of GSH, and IL‐10 level, with suppression of the antioxidant enzymes' activities. In addition, the gene expression of the hepatic inducible nitric oxide synthase (iNOS), and LAG‐3 were up‐regulated. Moreover, the protein expression of p‐PKC was up‐regulated, while that of PD‐1 and PD‐L1 were down‐regulated in the liver tissues of the HCC group. However, propranolol ameliorated the investigated parameters in the HCC/Prop group. Conclusion: Propranolol exhibited an anticancer effect and thus can be considered as a promising treatment for HCC. Blocking of PD‐1/PD‐L1 and LAG‐3 signals participated in the anti‐tumor effect of propranolol on HCC.
- Subjects
ASPARTATE aminotransferase; LABORATORY rats; DRUG efficacy; HEPATOCELLULAR carcinoma; ANTINEOPLASTIC agents; NITRIC-oxide synthases
- Publication
Fundamental & Clinical Pharmacology, 2024, Vol 38, Issue 4, p742
- ISSN
0767-3981
- Publication type
Article
- DOI
10.1111/fcp.12990