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- W2892054361 abstract "Previous studies have demonstrated that the selective cyclooxygenase‐2 (COX‐2) inhibitor celecoxib shows efficacy against multiple cancers, including hepatocellular carcinoma. However, whether celecoxib is effective in alleviating steatosis during hepatocarcinogenesis is unknown. In a rapid hepatocellular carcinoma (HCC) mouse model established via hydrodynamic transfection of activated forms of AKT and c‐Met proto‐oncogenes, we investigated the antisteatotic and anticarcinogenic efficacy of celecoxib in vivo. Multiple HCC cell lines were employed for in vitro evaluation. Additionally, immunoblotting, immunohistochemistry, hematoxylin and eosin staining and Oil Red O staining were applied for mechanistic investigation. The results revealed that if celecoxib was administered in the early stage of AKT/c‐Met‐induced HCC, it resulted in disease stabilization. Moreover, celecoxib could alleviate lipid accumulation in the HCC mice and in an oleic acid‐induced in vitro hepatic steatosis model. Further evidence at the molecular level indicated that celecoxib down‐regulated the expression of phospho‐ERK (Thr202/Tyr204) and proliferating cell nuclear antigen (PCNA) in the HCC mice. In addition, celecoxib efficiently repressed the phosphor‐Akt (Thr308)/fatty acid synthase (FASN) axis both in vivo and in vitro. Altogether, this study suggests that celecoxib exerts its antilipogenic efficacy by targeting a COX‐2/AKT/FASN cascade, which contributes to its ability to delay hepatocarcinogenesis." @default.
- W2892054361 created "2018-09-27" @default.
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- W2892054361 date "2018-09-20" @default.
- W2892054361 modified "2023-10-18" @default.
- W2892054361 title "Celecoxib alleviates AKT/c‐Met‐triggered rapid hepatocarcinogenesis by suppressing a novel COX‐2/AKT/FASN cascade" @default.
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- W2892054361 doi "https://doi.org/10.1002/mc.22904" @default.
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