期刊
CURRENT MOLECULAR PHARMACOLOGY
卷 15, 期 1, 页码 252-262出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1874467214666210708103752
关键词
Apoptosis; DENA; etoricoxib; hepatocellular carcinoma; inflammation; nonalcoholic fatty liver disease
资金
- Al Jalila Foundation, United Arab Emirates [AJF2018050]
This study aimed to investigate the chemopreventive effect of etoricoxib on DENA/2AAF-induced HCC in male Wistar rats. The results demonstrated that etoricoxib possesses an anticancer effect through its antioxidant, anti-inflammatory, and modulation of NF-KB/COX-2/PGE2 signaling.
Background: Liver cancer ranks as the 7th and 5th leading cause of cancer morbidity worldwide in men and women, respectively. Hepatocellular Carcinoma (HCC) is the most common type of liver cancer and is associated with an increasing global burden of Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH). Objective: The present study aimed to investigate the possible chemopreventive effect of etoricoxib on diethylnitrosamine (DENA) and 2-acetylaminofluorene (2AAF)-induced HCC in male Wistar rats. Methods: HCC was induced by DENA (150 mg/kg/week; i.p) for 2 weeks, then 2AAF (20 mg/kg; p.o) every other day for three successive weeks. Etoricoxib (0.6 mg/kg, p.o.) was given to DENA/2AAF-administered rats for 20 weeks. Results: Etoricoxib significantly suppressed alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19.9) as liver tumor biomarkers. It also decreased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels while increased serum albumin levels. Besides, it alleviated DENA/2AAF-induced histopathological abrasions and inflammatory cell infiltration. Furthermore, etoricoxib showed a potent antioxidant effect, supported by a significant lipid peroxide reduction and elevation in superoxide dismutase activity and GSH content. In addition, Etoricoxib significantly down-regulated the protein expression of interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), nuclear Factor-kappa B (NF-KB), phosphorylated nuclear Factor-kappa B (p-NF-KB), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). Conclusion: In conclusion, the current results proved that etoricoxib possesses an anticarcinogenic effect via its antioxidant, anti-inflammatory, and modulation of NF-KB/COX-2/PGE2 signaling.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据