Melatonin Mitigates the Progression of Chemically Induced Hepatocellular Carcinoma in Rats via Targeting Wnt/Β-Catenin Pathway, and Small Noncoding miR-let-7b.

IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Nesma Mohammed Bahaa Eldeen, Moataz Maher Kamel, Abbas Mohamed, Samaa Samir Kamar, Laila Rashed, Asmaa Mohammed ShamsEldeen
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Abstract

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.

褪黑素通过靶向 Wnt/Β-Catenin 通路和小非编码 miR-let-7b 缓解化学诱导的大鼠肝细胞癌的进展
背景:褪黑激素是控制睡眠-觉醒周期的激素,因其在免疫调节、抗炎和促进细胞凋亡方面的作用而备受关注。Wnt/β-catenin 信号可通过促进细胞分裂和迁移来调节癌症的进展,而 miR-let-7b 则可通过影响适应性免疫细胞的功能来抑制细胞的生长、迁移和侵袭。本研究旨在检测褪黑素作为一种免疫调节治疗方法对控制化学诱导的肝细胞癌(HCC)进展的影响:将 30 只雄性大鼠平均分为对照组、HCC 组和褪黑素-HCC 组。HCC 组和褪黑素-HCC 组的大鼠先腹腔注射二乙基亚硝胺(单剂量),然后重复皮下注射四氯化碳,每周一次,连续注射六周。褪黑素从研究的第一周开始给药,并在诱导 HCC 的过程中持续给药:结果:HCC组中,肿瘤坏死因子-α(TNF-α)、血管内皮生长因子(VEGF)和Wnt/β-catenin的表达水平显著升高,而microRNA Let7b则出现下调。服用褪黑素可逆转这些变化,同时增加肝脏中白细胞介素-2(IL-2)和Caspase-3的含量:结论:褪黑素除了具有促凋亡和抗血管生成的作用外,还能产生肝脏免疫调节变化,这分别体现在 IL-2、caspase-3 含量的增加和血管内皮生长因子水平的降低上。此外,在肝癌发生过程中使用褪黑激素能显著调节微RNA let7b和Wnt/β-catenin的表达。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Reports of Biochemistry and Molecular Biology
Reports of Biochemistry and Molecular Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
2.80
自引率
23.50%
发文量
60
审稿时长
10 weeks
期刊介绍: The Reports of Biochemistry & Molecular Biology (RBMB) is the official journal of the Varastegan Institute for Medical Sciences and is dedicated to furthering international exchange of medical and biomedical science experience and opinion and a platform for worldwide dissemination. The RBMB is a medical journal that gives special emphasis to biochemical research and molecular biology studies. The Journal invites original and review articles, short communications, reports on experiments and clinical cases, and case reports containing new insights into any aspect of biochemistry and molecular biology that are not published or being considered for publication elsewhere. Publications are accepted in the form of reports of original research, brief communications, case reports, structured reviews, editorials, commentaries, views and perspectives, letters to authors, book reviews, resources, news, and event agenda.
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