过量果糖摄入通过调控脂质代谢促进肝细胞癌的发生与进展OACSTPCD

Objective:Studies have confirmed that there is a potential link between excessive fructose intake and lipid metabolism disorders in liver,but the important role of this regulation in the development of liver cancer has not been fully revealed.The purpose of this study was to explore the effect and potential mechanism of excessive fructose intake on the pro-gression of liver cancer.Methods:We used a liver cancer mice model induced by intraperitoneal injection of N-nitrosodieth-ylamine(DEN)and carbon tetrachloride(CCl4),established an excessive fructose intake model via oral fructose solution,and a research system via a liver cancer cell line.Histopathological analysis and immunohistochemical staining were employed to analyze the impact of excessive fructose intake on mouse hepatic tissue.Cell counting kit-8 proliferation assay,scratch as-say and Transwell invasion assay were applied to evaluate the proliferation,migration,and invasion capabilities of liver cancer cells.Western blot were used to study the relative expression of enzymes involved in fatty acid synthesis metabolism.Results:Compared with the control group,the cancer of mice liver in the high fructose intake group was obvious,the tumor area signifi-cantly increased(P＜0.010),and the staining intensity of tumor proliferation index(Ki-67)significantly increased(P＜0.001).The results of Oil Red O staining and quantitative analysis showed that lipid accumulation in the liver of mice in the high fructose intake group was significantly higher than that in control group(P＜0.001).The results of these animal experi-ments suggested that excessive intake of exogenous fructose promoted liver cancer progression and lipid accumulation in a DEN+CC14 induced mice liver cancer model.The results of cell experiments showed that excessive fructose intake could pro-mote the proliferation,migration and invasion of hepatocellular carcinoma cell line HepG2(P＜0.010).Western blot results showed that the expression levels of acetyl-CoA carboxylase,fatty acid synthase and stearoyl-CoA desaturase-1 in HepG2 cells significantly increased(P＜0.010)after fructose treatment,and the expression of peroxisome proliferator-activated receptor alpha decreased(P＜0.010).Conclusion:Fructose may affect the progression of liver cancer by changing the key enzymes of fatty acid synthesis and metabolism,that is,up-regulating the expression of ACC,FAS and SCD1 and down-regulating the expression of PPARalpha to regulate lipid metabolism.