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Volume 12, Issue 3 (Vol.12 No.3 Oct 2023)
rbmb.net 2023, 12(3): 403-414 |
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Bahaa Eldeen N M, Kamel M M, Mohamed A, Kamar S S, Rashed L, Shams Eldeen A M. Melatonin Mitigates the Progression of Chemically Induced Hepatocellular Carcinoma in Rats via Targeting Wnt/Β-Catenin Pathway, and Small Noncoding miR-let-7b. rbmb.net 2023; 12 (3) :403-414
URL: http://rbmb.net/article-1-1284-en.html
URL: http://rbmb.net/article-1-1284-en.html
Nesma Mohammed Bahaa Eldeen 
, Moataz Maher Kamel , Abbas Mohamed , Samaa Samir Kamar , Laila Rashed , Asmaa Mohammed Shams Eldeen *
, Moataz Maher Kamel , Abbas Mohamed , Samaa Samir Kamar , Laila Rashed , Asmaa Mohammed Shams Eldeen *
Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Abstract: (447 Views)
Background: Melatonin, the controlling hormone of the sleep–wake cycle, has acquired attention due to its role in immunomodulation, anti-inflammation, as well as its proapoptotic effects. Wnt/β-catenin signaling can modulate cancer progression by promoting cell division and migration, while miR-let-7b may inhibit cell growth, migration, and invasion by affecting the function of adaptive immune cells. This work was designed to detect the effect of using melatonin as an immunomodulating therapeutic approach to control the progression of chemically induced hepatocellular carcinoma (HCC).
Methods: Thirty male rats were equally divided into control, HCC, and melatonin-HCC groups. Animals in the HCC and melatonin-HCC groups were injected with diethylnitrosamine (intraperitoneal single dose) followed by repeated carbon-tetrachloride subcutaneous injection once weekly for six weeks. Melatonin was given from the first week of the study and continued during the process of HCC induction.
Results: In the HCC group, the levels of tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and Wnt/β-catenin expression significantly increased, while there was a downregulation of microRNA Let7b. Melatonin administration reversed these changes, along with an increase in hepatic content of interleukin-2 (IL-2) and caspase-3.
Conclusions: Melatonin exerted hepatic immunomodulating changes, in addition to proapoptotic and antiangiogenic effects, illustrated by increased IL-2, caspase-3, and decreased VEGF levels, respectively. Moreover, the use of melatonin during hepatocarcinogenesis positively modulated the disrupted expression of microRNA let7b and Wnt/β-catenin significantly.
Methods: Thirty male rats were equally divided into control, HCC, and melatonin-HCC groups. Animals in the HCC and melatonin-HCC groups were injected with diethylnitrosamine (intraperitoneal single dose) followed by repeated carbon-tetrachloride subcutaneous injection once weekly for six weeks. Melatonin was given from the first week of the study and continued during the process of HCC induction.
Results: In the HCC group, the levels of tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and Wnt/β-catenin expression significantly increased, while there was a downregulation of microRNA Let7b. Melatonin administration reversed these changes, along with an increase in hepatic content of interleukin-2 (IL-2) and caspase-3.
Conclusions: Melatonin exerted hepatic immunomodulating changes, in addition to proapoptotic and antiangiogenic effects, illustrated by increased IL-2, caspase-3, and decreased VEGF levels, respectively. Moreover, the use of melatonin during hepatocarcinogenesis positively modulated the disrupted expression of microRNA let7b and Wnt/β-catenin significantly.
Type of Article: Original Article |
Subject:
Immunology
Received: 2023/11/9 | Accepted: 2024/01/2 | Published: 2024/02/25
Received: 2023/11/9 | Accepted: 2024/01/2 | Published: 2024/02/25
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