Zhang, Cong; Sheng, Lei; Yuan, Ming; Hu, Junjie; Meng, Yan; Wu, Yong; Chen, Liang; Yu, Huifan; Li, Shan; Zheng, Guohua; Qiu, Zhenpeng published the artcile< Orlistat delays hepatocarcinogenesis in mice with hepatic co-activation of AKT and c-Met>, Reference of 96829-58-2, the main research area is orlistat AKT cMet hepatic carcinoma antitumor agent; Fatty acid synthase; Hepatocarcinogenesis; Lipogenesis; Orlistat; Proliferation.
Orlistat (Xenical), a US Food and Drug Administration (FDA)-approved anti-obesity drug, shows efficacy against multiple tumor types, including hepatocellular carcinoma (HCC), due to its ability to inhibit fatty acid synthase (FASN) activity. However, whether orlistat affects hepatocellular malignant transformation during hepatocarcinogenesis in vivo is unknown. This study assessed the antisteatotic and antitumorigenic efficacy of orlistat in a rapid HCC FVB/N mouse model established via hydrodynamic transfection of activated forms of AKT and c-Met proto-oncogenes. Human hepatoma cell lines were used for mech. validation in vitro. Hematoxylin and eosin staining, immunohistochem., and immunoblotting were applied for the mechanistic investigation. The results revealed that when orlistat was administered in the early stage of AKT/c-Met-triggered hepatocarcinogenesis, it resulted in the elimination of hepatic tumor burden. Mechanistically, orlistat efficiently elevated PTEN expression and suppressed AKT/SREBP1/FASN signaling both in vivo and in vitro, impairing AKT/c-Met-driven de novo lipogenesis and aberrant proliferation. Altogether, this study demonstrates the antilipogenic and antiproliferative efficacy of orlistat in hepatocarcinogenesis, suggesting that orlistat may be beneficial for the treatment of HCC, especially in NAFLD-related HCCs featuring activated AKT/mTOR cascade and increased lipogenesis in livers.
Toxicology and Applied Pharmacology published new progress about Antitumor agents. 96829-58-2 belongs to class amides-buliding-blocks, and the molecular formula is C29H53NO5, Reference of 96829-58-2.
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