关键词:  , 癌, 肝细胞, 脂代谢障碍, 奥利司他

Abstract: Objective To explore the function of fatty acid synthase (FASN) in the progression of hepatocellular carcinoma (HCC), in order to provide a favorable theoretical basis for the treatment of HCC. 
Methods The expression and enrichment pathway of FASN in HCC tumor tissues were analyzed by bioinformatics. Cell Counting Kit-8 (CCK-8), colony formation and flow cytometry were used to detect cell viability, proliferation and apoptosis, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the level of FASN. The expression of BCL2-associated X (Bax) and B-cell lymphoma-2 (Bcl-2) was detected by Western blot. Lipophilic fluorescent dye BODIPY 493/503 was used to detect the accumulation of neutral lipids, and the levels of free fatty acids and glycerol were detected by reagent kit. 
Results The expression of FASN in HCC tumor tissue was higher than that in paracancerous tissues. Based on verification in an in vitro cell model, the results showed that compared with MIHA cells, the expression of FASN was significantly upregulated in HCC cell lines (Huh-7, HepG2, Hep3B) (P＜0.05). Compared with the control group, the expression of FASN decreased in cells in the si-FASN group, but increased in the oe-FASN group (P＜0.05). Compared with the control group, the si-FASN group showed a decrease in HepG2 cell viability and clone count, while the oe-FASN group showed an increase in Hep3B cell viability and clone count (P＜0.05). Compared with the control group, the apoptosis rate of HepG2 cells increased in the si-FASN group, but decreased in the oe-FASN group (P＜0.05). Compared with the control group, the si-FASN group showed an increase in Bax expression and a decrease in Bcl-2 expression in cells. The expression of Bax decreased and the expression of Bcl-2 increased in the oe-FASN group cells (P＜0.05). Compared with the control group, the neutral lipid content decreased in the si-FASN group, but increased in the oe-FASN group (P＜0.05). Compared with the control group, the levels of free fatty acids and glycerol decreased in the si-FASN group but increased in the oe-FASN group (P＜0.05). Compared with the oe-NC+DMSO group, the expression of FASN decreased in the oe-NC+Orlistat group cells decreased, while compared with the oe-NC+Orlistat group, the expression of FASN in the oe-FASN+Orlistat group cells increased (P＜0.05). Compared with the oe-NC+DMSO group, the proliferation level of cells in the oe-NC+Orlistat group decreased and apoptosis was induced. Compared with the oe-NC+Orlistat group, the oe-FASN+Orlistat group showed increased cell proliferation and inhibited cell apoptosis (P＜0.05). Compared with the oe-NC+DMSO group, the expression of pro-apoptotic factor Bax increased in cells of the oe-NC+Orlistat group, while the expression of anti apoptotic factor Bcl-2 was reduced. Compared with the oe-NC+Orlistat group, the expression of pro-apoptotic factor Bax in the Orlistat+oe FASN group cells significantly reduced, while the expression of anti-apoptotic factor Bcl-2 increased (P＜0.05). Compared with the oe-NC+DMSO group, the neutral lipid content, free fatty acid level, and glycerol level in the oe-NC+Orlistat group cells reduced.  Compared with the oe-NC+Orlistat group, the neutral lipid content, free fatty acid level, and glycerol level in the oe-FASN+Orlistat group cells increased (P＜0.05). 
Conclusion The results of this study emphasize the role of FASN in the promotion of HCC progression and lipid metabolism. The fatty acid synthase inhibitor Orlistat can inhibit FASN expression, which can inhibit HCC progression by regulating reprogramming in fatty acid metabolism.

Key words: carcinoma, hepatocellular, lipid metabolism disorders, Orlistat