Department of Molecular and Cell Biology, Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD, 4811, Australia.
Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, 2145, Australia.
Sci Rep. 2020 Oct 7;10(1):16769. doi: 10.1038/s41598-020-73653-5.
Hepatocellular carcinoma is rapidly becoming one of the leading causes of cancer-related deaths, largely due to the increasing incidence of non-alcoholic fatty liver disease. This in part may be attributed to Westernised diets high in fructose sugar. While many studies have shown the effects of fructose on inducing metabolic-related liver diseases, little research has investigated the effects of fructose sugar on liver cancer metabolism. The present study aimed to examine the metabolic effects of fructose on hepatocellular carcinoma growth in vitro and in vivo. Fructose sugar was found to reduce cell growth in vitro, and caused alterations in the expression of enzymes involved in the serine-glycine synthesis and pentose phosphate pathways. These biosynthesis pathways are highly active in cancer cells and they utilise glycolytic by-products to produce energy and nucleotides for growth. Hence, the study further investigated the efficacy of two novel drugs that inhibit these pathways, namely NCT-503 and Physcion. The study is the first to show that the combination treatment of NCT-503 and Physcion substantially inhibited hepatocellular carcinoma growth in vitro and in vivo. The combination of fructose diet and metabolism-inhibiting drugs may provide a unique metabolic environment that warrants further investigation in targeting hepatocellular carcinoma.
肝细胞癌正在迅速成为癌症相关死亡的主要原因之一，主要是由于非酒精性脂肪性肝病的发病率不断上升。这在一定程度上可能归因于富含果糖糖的西式饮食。虽然许多研究已经表明果糖对诱导代谢相关肝病的影响，但很少有研究调查果糖糖对肝癌代谢的影响。本研究旨在研究果糖对肝癌细胞体外和体内生长的代谢影响。果糖糖被发现可减少体外细胞生长，并导致参与丝氨酸-甘氨酸合成和戊糖磷酸途径的酶的表达发生改变。这些生物合成途径在癌细胞中非常活跃，它们利用糖酵解的副产物来产生能量和核苷酸以促进生长。因此，该研究进一步调查了两种抑制这些途径的新型药物 NCT-503 和大黄素的疗效。这项研究首次表明，NCT-503 和大黄素的联合治疗可显著抑制肝癌细胞的体外和体内生长。果糖饮食和代谢抑制药物的联合治疗可能提供了一种独特的代谢环境，值得进一步研究以靶向肝癌。
